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Professor Inês Barroso

Professor of Diabetes

+44 (0) 1392 408221

RILD Building

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Inês obtained her BSc (“Licenciatura”) degree in Biology from the University of Lisbon (1992), before moving to the University of Cambridge where she was awarded a PhD in Human Molecular Genetics (1996). After her PhD, she was a founding scientist at a start-up biotechnology company (Hexagen, later bought by Incyte) where she became Director of Diabetes Target Validation. In 2002, Inês moved to the Wellcome Trust Sanger Institute where she worked for 16 years, which included serving as Head of the Human Genetics programme for 6 years. Prior to joining the University of Exeter (Jan 2020), she spent a year at the MRC Epidemiology Unit as Director of Research, Mechanisms of Metabolic Disease.

Inês has over 20 years of experience in the field of human genetics applied to human disease. With more than 200 peer-reviewed publications and book chapters, she is ranked as one of the most cited researchers in her field. Her research traverses both the monogenic and polygenic fields and focuses on the genetic aetiology and mechanisms of type 2 diabetes, obesity, rare forms of these conditions (e.g. childhood onset obesity and syndromes of insulin action), and related quantitative traits. With collaborators, she has discovered many of the genes underpinning syndromes of insulin resistance, as well as being involved in obesity gene discovery, or mouse follow-up studies. Since 2009, she has led MAGIC (Meta-Analysis of Glucose and Insulin-related traits Consortium), a consortium meta-analysing genome-wide association studies to uncover loci associated with glycaemic traits. Within the context of MAGIC, her group has identified the vast majority of established loci influencing glycaemic measures within healthy physiological range. In addition to her genetic research, Inês is undertaking further genomic, biological and physiological studies to shed light on the aetiology, mechanisms and biology of type 2 diabetes.

Qualifications

2003 – MSc, Genetic Epidemiology, University of Pavia, Italy
1996 – PhD, Human Molecular Genetics, University of Cambridge, UK
1992 – BSc. (“Licenciatura”), Biology, University of Lisbon, Portugal

Research

Research interests

Inês leads a diverse, multidisciplinary team which focuses on identifying new genes and loci involved in type 2 diabetes, obesity and related traits particularly, HbA1c. Ultimately her aim is to take those discoveries into new understanding of the mechanisms and biology underlying type 2 diabetes and obesity.

She is interested in using genetics to improve diabetes diagnosis and prediction, and to use epigenetic marks and genetics to improve understanding of disease genes and pathways. To do this, Inês’ research combines both genomic data and computational approaches to link genetic variants and genes to function and biological pathways.

Inês strongly believes in creating an environment where people of diverse skills, cultures and background can all work together to achieve their goals. She welcomes enquiries from potential interested applicants to join the group.

Research projects

Current Projects:

Genome-wide multi-ancestry analyses of glycaemic traits
Multi-ancestry fine-mapping of glycaemic loci
Investigation of new genes and pathways involved in obesity and glycaemic traits related to type 2 diabetes
From variant to function – uncovering the cells, tissues and biological pathways impacted by glycaemic trait association loci and how they may influence type 2 diabetes risk
Impact of genetic variation on type 2 diabetes risk, diagnosis and complications in ancestrally diverse populations
Use of HbA1c and associated genetic variants to improve type 2 diabetes diagnoses

Publications

Journal articles

Barroso I, Feetham CH, Mokrosiński J, Lawler K, Keogh JM, Henning E, Mendes de Oliveira E, Ayinampudi V, Saeed S, Bonnefond A, et al (In Press). A rare human variant that disrupts GPR10 signalling causes weight gain in mice. Nature Communications

Young KG, McGovern AP, Barroso I, Hattersley AT, Jones AG, Shields BM, Thomas NJ, Dennis JM (2023). Correction to: the impact of population-level HbA1c screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis. Diabetologia, 66(8). Author URL.

Mason JH, Luo L, Reinwald Y, Taffetani M, Hallas-Potts A, Herrington CS, Srsen V, Lin C-J, Barroso IA, Zhang Z, et al (2023). Debiased ambient vibrations optical coherence elastography to profile cell, organoid and tissue mechanical properties. COMMUNICATIONS BIOLOGY, 6(1). Author URL.

Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, et al (2023). GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification. Nature Genetics, 55(9), 1448-1461. Abstract.

Li JH, Brenner LN, Kaur V, Figueroa K, Schroeder P, Huerta-Chagoya A, Chen J, Spracklen CN, Marenne G, Varshney A, et al (2023). Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH. Diabetologia, 66(7), 1260-1272.

Aims/hypothesis: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes. Methods: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between genetic variants and primary endpoints of drug response. In a more focused analysis, we evaluated the influence of 804 unique type 2 diabetes- and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalisation analyses to identify shared genetic signals. Results: Five genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency [MAFAfr]=0.0283) at rs149403252 and lower fasting glucose at Visit 2 following metformin (p=1.9×10−9); carriers were found to have a 0.94 mmol/l larger decrease in fasting glucose. rs111770298, another African ancestry-specific variant (MAFAfr=0.0536), was associated with a reduced response to metformin (p=2.4×10−8), where carriers had a 0.29 mmol/l increase in fasting glucose compared with non-carriers, who experienced a 0.15 mmol/l decrease. This finding was validated in the Diabetes Prevention Program, where rs111770298 was associated with a worse glycaemic response to metformin: heterozygous carriers had an increase in HbA1c of 0.08% and non-carriers had an HbA1c increase of 0.01% after 1 year of treatment (p=3.3×10−3). We also identified associations between type 2 diabetes-associated variants and glycaemic response, including the type 2 diabetes-protective C allele of rs703972 near ZMIZ1 and increased levels of active glucagon-like peptide 1 (GLP-1) (p=1.6×10−5), supporting the role of alterations in incretin levels in type 2 diabetes pathophysiology. Conclusions/interpretation: We present a well-phenotyped, densely genotyped, multi-ancestry resource to study gene–drug interactions, uncover novel variation associated with response to common glucose-lowering medications and provide insight into mechanisms of action of type 2 diabetes-related variation. Data availability: the complete summary statistics from this study are available at the Common Metabolic Diseases Knowledge Portal (https://hugeamp.org) and the GWAS Catalog (www.ebi.ac.uk/gwas/ , accession IDs: GCST90269867 to GCST90269899). Graphical Abstract: [Figure not available: see fulltext.]

Abstract.

Williamson A, Norris DM, Yin X, Broadaway KA, Moxley AH, Vadlamudi S, Wilson EP, Jackson AU, Ahuja V, Andersen MK, et al (2023). Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake. Nat Genet, 55(6), 973-983. Abstract. Author URL.

Young KG, McGovern AP, Barroso I, Hattersley AT, Jones AG, Shields BM, Thomas NJ, Dennis JM (2023). HbA1c screening for the diagnosis of diabetes. Reply to Brož J, Brabec M, Krollová P et al [letter]. Diabetologia, 66(8), 1578-1579. Author URL.

Broadaway KA, Yin X, Williamson A, Parsons VA, Wilson EP, Moxley AH, Vadlamudi S, Varshney A, Jackson AU, Ahuja V, et al (2023). Loci for insulin processing and secretion provide insight into type 2 diabetes risk. Am J Hum Genet, 110(2), 284-299. Abstract. Author URL.

Riveros-Mckay F, Roberts D, Di Angelantonio E, Yu B, Soranzo N, Danesh J, Selvin E, Butterworth AS, Barroso I (2022). An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript. Diabetes, 71(2), 359-364. Abstract. Author URL.

Murphy N, Song M, Papadimitriou N, Carreras-Torres R, Langenberg C, Martin RM, Tsilidis KK, Barroso I, Chen J, Frayling TM, et al (2022). Associations Between Glycemic Traits and Colorectal Cancer: a Mendelian Randomization Analysis. J Natl Cancer Inst, 114(5), 740-752. Abstract. Author URL.

He Y, Brouwers B, Liu H, Liu H, Lawler K, Mendes de Oliveira E, Lee D-K, Yang Y, Cox AR, Keogh JM, et al (2022). Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior. Nat Med, 28(12), 2537-2546. Abstract. Author URL.

Koprulu M, Zhao Y, Wheeler E, Dong L, Rocha N, Li C, Griffin JD, Patel S, Van de Streek M, Glastonbury CA, et al (2022). Identification of Rare Loss-of-Function Genetic Variation Regulating Body Fat Distribution. J Clin Endocrinol Metab, 107(4), 1065-1077. Abstract. Author URL.

Kuchenbaecker K, Gilly A, Suveges D, Southam L, Giannakopoulou O, Kilian B, Tsafantakis E, Karaleftheri M, Farmaki A-E, Gurdasani D, et al (2022). Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations. Sci Rep, 12(1). Abstract. Author URL.

Young KG, McGovern AP, Barroso I, Hattersley AT, Jones AG, Shields BM, Thomas NJ, Dennis JM (2022). The impact of population-level HbA1c screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis. Diabetologia, 66(2), 300-309.

Abstract
. Aims/hypothesis
. Screening programmes can detect cases of undiagnosed diabetes earlier than symptomatic or incidental diagnosis. However, the improvement in time to diagnosis achieved by screening programmes compared with routine clinical care is unclear. We aimed to use the UK Biobank population-based study to provide the first population-based estimate of the reduction in time to diabetes diagnosis that could be achieved by HbA1c-based screening in middle-aged adults.
.
. Methods
. We studied UK Biobank participants aged 40–70 years with HbA1c measured at enrolment (but not fed back to participants/clinicians) and linked primary and secondary healthcare data (n=179,923) and identified those with a pre-existing diabetes diagnosis (n=13,077, 7.3%). Among the remaining participants (n=166,846) without a diabetes diagnosis, we used an elevated enrolment HbA1c level (≥48 mmol/mol [≥6.5%]) to identify those with undiagnosed diabetes. For this group, we used Kaplan–Meier analysis to assess the time between enrolment HbA1c measurement and subsequent clinical diabetes diagnosis up to 10 years, and Cox regression to identify clinical factors associated with delayed diabetes diagnosis.
.
. Results
. In total, 1.0% (1703/166,846) of participants without a diabetes diagnosis had undiagnosed diabetes based on calibrated HbA1c levels at UK Biobank enrolment, with a median HbA1c level of 51.3 mmol/mol (IQR 49.1–57.2) (6.8% [6.6–7.4]). These participants represented an additional 13.0% of diabetes cases in the study population relative to the 13,077 participants with a diabetes diagnosis. The median time to clinical diagnosis for those with undiagnosed diabetes was 2.2 years, with a median HbA1c at clinical diagnosis of 58.2 mmol/mol (IQR 51.0–80.0) (7.5% [6.8–9.5]). Female participants with lower HbA1c and BMI measurements at enrolment experienced the longest delay to clinical diagnosis.
.
. Conclusions/interpretation
. Our population-based study shows that HbA1c screening in adults aged 40–70 years can reduce the time to diabetes diagnosis by a median of 2.2 years compared with routine clinical care. The findings support the use of HbA1c screening to reduce the time for which individuals are living with undiagnosed diabetes.
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. Graphical abstract
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Abstract.

Hess JL, Tylee DS, Mattheisen M, Adolfsson R, Agartz I, Agerbo E, Albus M, Alexander M, Amin F, Andreassen OA, et al (2021). A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry, 26(3), 800-815. Abstract.

Cuellar-Partida G, Tung JY, Eriksson N, Albrecht E, Aliev F, Andreassen OA, Barroso I, Beckmann JS, Boks MP, Boomsma DI, et al (2021). Genome-wide association study identifies 48 common genetic variants associated with handedness. Nat Hum Behav, 5(1), 59-70. Abstract. Author URL.

de Oliveira EM, Keogh JM, Talbot F, Henning E, Ahmed R, Perdikari A, Bounds R, Wasiluk N, Ayinampudi V, Barroso I, et al (2021). Obesity-Associated GNAS Mutations and the Melanocortin Pathway. NEW ENGLAND JOURNAL OF MEDICINE, 385(17), 1581-1592. Author URL.

Agrawal N, Lawler K, Davidson CM, Keogh JM, Legg R, INTERVAL, Barroso I, Farooqi IS, Brand AH (2021). Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila. PLoS Biol, 19(11). Abstract. Author URL.

Lagou V, Mägi R, Hottenga J-J, Grallert H, Perry JRB, Bouatia-Naji N, Marullo L, Rybin D, Jansen R, Min JL, et al (2021). Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nat Commun, 12(1). Author URL.

Lagou V, Mägi R, Hottenga J-J, Grallert H, Perry JRB, Bouatia-Naji N, Marullo L, Rybin D, Jansen R, Min JL, et al (2021). Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nat Commun, 12(1). Abstract. Author URL.

Hernandez N, Soenksen J, Newcombe P, Sandhu M, Barroso I, Wallace C, Asimit JL (2021). The flashfm approach for fine-mapping multiple quantitative traits. NATURE COMMUNICATIONS, 12(1). Author URL.

Barroso I (2021). The importance of increasing population diversity in genetic studies of type 2 diabetes and related glycaemic traits. Diabetologia, 64(12), 2653-2664. Abstract. Author URL.

Chen J, Spracklen CN, Marenne G, Varshney A, Corbin LJ, Luan J, Willems SM, Wu Y, Zhang X, Horikoshi M, et al (2021). The trans-ancestral genomic architecture of glycemic traits. Nat Genet, 53(6), 840-860. Abstract. Author URL.

Kamitaki N, Sekar A, Handsaker RE, de Rivera H, Tooley K, Morris DL, Taylor KE, Whelan CW, Tombleson P, Loohuis LMO, et al (2020). Complement genes contribute sex-biased vulnerability in diverse disorders. Nature, 582(7813), 577-581.

Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren’s syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren’s syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3–6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren’s syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren’s syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren’s syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women’s greater risk of SLE and Sjögren’s syndrome and men’s greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.

Abstract.

Sallah N, Miley W, Labo N, Carstensen T, Fatumo S, Gurdasani D, Pollard MO, Dilthey AT, Mentzer AJ, Marshall V, et al (2020). Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections. Nature Communications, 11(1). Abstract.

Marenne G, Hendricks AE, Perdikari A, Bounds R, Payne F, Keogh JM, Lelliott CJ, Henning E, Pathan S, Ashford S, et al (2020). Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription. Cell Metab, 31(6), 1107-1119.e12. Abstract. Author URL.

Cai L, Wheeler E, Kerrison ND, Luan J, Deloukas P, Franks PW, Amiano P, Ardanaz E, Bonet C, Fagherazzi G, et al (2020). Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study. Sci Data, 7(1). Abstract. Author URL.

Sonoyama T, Stadler LKJ, Zhu M, Keogh JM, Henning E, Hisama F, Kirwan P, Jura M, Blaszczyk BK, DeWitt DC, et al (2020). Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities. Sci Rep, 10(1). Abstract. Author URL.

Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, Scholz M, van der Most PJ, Monnereau C, Stergiakouli E, et al (2020). Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genet, 16(10). Abstract. Author URL.

Riveros-Mckay F, Oliver-Williams C, Karthikeyan S, Walter K, Kundu K, Ouwehand WH, Roberts D, Di Angelantonio E, Soranzo N, Danesh J, et al (2020). The influence of rare variants in circulating metabolic biomarkers. PLoS Genet, 16(3). Abstract. Author URL.

Moore R, Casale FP, Jan Bonder M, Horta D, BIOS Consortium, Franke L, Barroso I, Stegle O (2019). A linear mixed-model approach to study multivariate gene-environment interactions. Nat Genet, 51(1), 180-186. Abstract. Author URL.

De Franco E, Flanagan S, Caswell R, Ellard S, Hattersley A, Watson RA, Weninger WJ, Wong CC, Caswell R, Green A, et al (2019). A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development. American Journal of Human Genetics

Nik-Zainal S, Barroso I (2019). Bullying investigations need a code of conduct. Nature, 565(7740). Author URL.

Romagnoni A, Jégou S, Van Steen K, Wainrib G, Hugot JP, Peyrin-Biroulet L, Chamaillard M, Colombel JF, Cottone M, D’Amato M, et al (2019). Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data. Scientific Reports, 9(1). Abstract.

Iglesias AI, Mishra A, Vitart V, Bykhovskaya Y, Hoehn R, Springelkamp H, Cuellar-Partida G, Gharahkhani P, Bailey JNC, Willoughby CE, et al (2019). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases (vol 9, 1864, 2018). NATURE COMMUNICATIONS, 10 Author URL.

Flores A, Argetsinger LS, Stadler LKJ, Malaga AE, Vander PB, DeSantis LC, Joe RM, Cline JM, Keogh JM, Henning E, et al (2019). Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance. DIABETES, 68(11), 2049-2062. Author URL.

Karasik D, Zillikens MC, Hsu Y-H, Aghdassi A, Akesson K, Amin N, Barroso I, Bennett DA, Bertram L, Bochud M, et al (2019). Disentangling the genetics of lean mass. Am J Clin Nutr, 109(2), 276-287. Abstract. Author URL.

Marenne G, Hendricks A, Perdikari A, Bounds R, Payne F, Keogh JM, Lelliott CJ, Henning E, Pathan S, Ashford S, et al (2019). Exome Sequencing Identifies Multiple Genes and Gene-Sets Contributing to Severe Childhood Obesity.

Riveros-McKay F, Mistry V, Bounds R, Hendricks A, Keogh JM, Thomas H, Henning E, Corbin LJ, Understanding Society Scientific Group, O'Rahilly S, et al (2019). Genetic architecture of human thinness compared to severe obesity. PLoS Genet, 15(1). Abstract. Author URL.

Liu C-T, Merino J, Rybin D, DiCorpo D, Benke KS, Bragg-Gresham JL, Canouil M, Corre T, Grallert H, Isaacs A, et al (2019). Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals. SCIENTIFIC REPORTS, 9 Author URL.

Chen J, Sun M, Adeyemo A, Pirie F, Carstensen T, Pomilla C, Doumatey AP, Chen G, Young EH, Sandhu M, et al (2019). Genome-wide association study of type 2 diabetes in Africa. DIABETOLOGIA, 62(7), 1204-1211. Author URL.

Gurdasani D, Barroso I, Zeggini E, Sandhu MS (2019). Genomics of disease risk in globally diverse populations. NATURE REVIEWS GENETICS, 20(9), 520-535. Author URL.

Gurdasani D, Barroso I, Zeggini E, Sandhu MS (2019). Genomics of disease risk in globally diverse populations (vol 20, pg 520, 2019). NATURE REVIEWS GENETICS, 20(9), 562-562. Author URL.

van der Klaauw AA, Croizier S, Mendes de Oliveira E, Stadler LKJ, Park S, Kong Y, Banton MC, Tandon P, Hendricks AE, Keogh JM, et al (2019). Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance. Cell, 176(4), 729-742.e18. Abstract. Author URL.

Haworth S, Shapland CY, Hayward C, Prins BP, Felix JF, Medina-Gomez C, Rivadeneira F, Wang C, Ahluwalia TS, Vrijheid M, et al (2019). Low-frequency variation in TP53 has large effects on head circumference and intracranial volume. Nature Communications, 10(1). Abstract.

Leong A, Chen J, Wheeler E, Hivert M-F, Liu C-T, Merino J, Dupuis J, Tai ES, Rotter JI, Florez JC, et al (2019). Mendelian Randomization Analysis of Hemoglobin A1c as a Risk Factor for Coronary Artery Disease. Diabetes Care, 42(7), 1202-1208. Abstract. Author URL.

Patsopoulos NA, Baranzini SE, Santaniello A, Shoostari P, Cotsapas C, Wong G, Beecham AH, James T, Replogle J, Vlachos IS, et al (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. SCIENCE, 365(6460), 1417-+. Author URL.

Harold D, Connolly S, Riley BP, Kendler KS, McCarthy SE, McCombie WR, Richards A, Owen MJ, O'Donovan MC, Walters JTR, et al (2019). Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 180(3), 223-231. Abstract.

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, et al (2019). Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet, 51(7), 1191-1192. Abstract. Author URL.

Yang Y, van der Klaauw AA, Zhu L, Cacciottolo TM, He Y, Stadler LKJ, Wang C, Xu P, Saito K, Hinton A, et al (2019). Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis. NATURE COMMUNICATIONS, 10 Author URL.

Barroso I, McCarthy MI (2019). The Genetic Basis of Metabolic Disease. CELL, 177(1), 146-161. Author URL.

Ng N, Willems SM, Fernandez J, Fine RS, Wheeler E, Wessel J, Kitajima H, Marenne G, Rundle JK, Sim X, et al (2019). Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation.

Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, et al (2019). Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa. CELL, 179(4), 984-+. Author URL.

Adeyemo AA, Zaghloul NA, Chen G, Doumatey AP, Leitch CC, Hostelley TL, Nesmith JE, Zhou J, Bentley AR, Shriner D, et al (2019). ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response. NATURE COMMUNICATIONS, 10 Author URL.

Barroso I (2018). ADCY3, neuronal primary cilia and obesity. Nat Genet, 50(2), 166-167. Author URL.

Gilly A, Suveges D, Kuchenbaecker K, Pollard M, Southam L, Hatzikotoulas K, Farmaki A-E, Bjornland T, Waples R, Appel EVR, et al (2018). Author Correction: Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits. Nat Commun, 9(1). Abstract. Author URL.

Gilly A, Suveges D, Kuchenbaecker K, Pollard M, Southam L, Hatzikotoulas K, Farmaki A-E, Bjornland T, Waples R, Appel EVR, et al (2018). Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits. Nat Commun, 9(1). Abstract. Author URL.

Iglesias AI, Mishra A, Vitart V, Bykhovskaya Y, Höhn R, Springelkamp H, Cuellar-Partida G, Gharahkhani P, Bailey JNC, Willoughby CE, et al (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nature Communications, 9(1). Abstract.

Logan CV, Murray JE, Parry DA, Robertson A, Bellelli R, Tarnauskaitė Ž, Challis R, Cleal L, Borel V, Fluteau A, et al (2018). DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency. Am J Hum Genet, 103(6), 1038-1044. Abstract. Author URL.

Huang T, Ding M, Bergholdt HKM, Wang T, Heianza Y, Sun D-J, Frazier-Wood AC, Aslibekyan S, North KE, Voortman T, et al (2018). Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies. CLINICAL CHEMISTRY, 64(1), 183-191. Author URL.

Barroso I, Florez JC (2018). Editorial overview: Molecular and genetic basis of [metabolic] disease: Genes, glucose, glycerol and girth: metabolism in our DNA. Curr Opin Genet Dev, 50, iv-vi. Author URL.

Flannick J, Fuchsberger C, Mahajan A, Teslovich TM, Agarwala V, Gaulton KJ, Caulkins L, Koesterer R, Ma C, Moutsianas L, et al (2018). Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data, 5 Abstract. Author URL.

Sallah N, Palser AL, Watson SJ, Labo N, Asiki G, Marshall V, Newton R, Whitby D, Kellam P, Barroso I, et al (2018). Genome-Wide Sequence Analysis of Kaposi Sarcoma-Associated Herpesvirus Shows Diversification Driven by Recombination. J Infect Dis, 218(11), 1700-1710. Abstract. Author URL.

Ruderfer DM, Ripke S, McQuillin A, Boocock J, Stahl EA, Pavlides JMW, Mullins N, Charney AW, Ori APS, Loohuis LMO, et al (2018). Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell, 173(7), 1705-1715.e16. Abstract.

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, et al (2018). Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet, 50(1), 26-41. Abstract. Author URL.

Hendricks AE, Billups SC, Pike HNC, Farooqi IS, Zeggini E, Santorico SA, Barroso I, Dupuis J (2018). ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls. PLoS Genet, 14(10). Abstract. Author URL.

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, et al (2018). Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet, 50(5), 766-767. Abstract. Author URL.

Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY, Gan W, Kitajima H, Taliun D, Rayner NW, et al (2018). Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet, 50(4), 559-571. Abstract. Author URL.

Manning A, Highland HM, Gasser J, Sim X, Tukiainen T, Fontanillas P, Grarup N, Rivas MA, Mahajan A, Locke AE, et al (2017). A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population is Associated with Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes, 66(7), 2019-2032. Abstract. Author URL.

Asimit JL, Payne F, Morris AP, Cordell HJ, Barroso I (2017). A two-stage inter-rater approach for enrichment testing of variants associated with multiple traits. Eur J Hum Genet, 25(3), 341-349. Abstract. Author URL.

Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M, Pervjakova N, Pers TH, Johnson AD, Eicher JD, et al (2017). An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes, 66(11), 2888-2902. Abstract. Author URL.

Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L, Winkler TW, Chu AY, Mahajan A, Hadley D, et al (2017). Correction: Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults. PLoS Genet, 13(8). Abstract. Author URL.

Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, et al (2017). Corrigendum: Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet, 49(2). Author URL.

Moir L, Bochukova EG, Dumbell R, Banks G, Bains RS, Nolan PM, Scudamore C, Simon M, Watson KA, Keogh J, et al (2017). Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety. Mol Metab, 6(11), 1419-1428. Abstract. Author URL.

Zillikens MC, Demissie S, Hsu Y-H, Yerges-Armstrong LM, Chou W-C, Stolk L, Livshits G, Broer L, Johnson T, Koller DL, et al (2017). Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun, 8(1). Abstract. Author URL.

Wheeler E, Marenne G, Barroso I (2017). Genetic aetiology of glycaemic traits: approaches and insights. Hum Mol Genet, 26(R2), R172-R184. Abstract. Author URL.

Justice AE, Winkler TW, Feitosa MF, Graff M, Fisher VA, Young K, Barata L, Deng X, Czajkowski J, Hadley D, et al (2017). Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun, 8 Abstract. Author URL.

Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L, Winkler TW, Chu AY, Mahajan A, Hadley D, et al (2017). Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults. PLoS Genet, 13(4). Abstract. Author URL.

Rocha N, Bulger DA, Frontini A, Titheradge H, Gribsholt SB, Knox R, Page M, Harris J, Payne F, Adams C, et al (2017). Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression. Elife, 6 Abstract. Author URL.

Leiter SM, Parker VER, Welters A, Knox R, Rocha N, Clark G, Payne F, Lotta L, Harris J, Guerrero-Fernández J, et al (2017). Hypoinsulinaemic, hypoketotic hypoglycaemia due to mosaic genetic activation of PI3-kinase. Eur J Endocrinol, 177(2), 175-186. Abstract. Author URL.

Wheeler E, Leong A, Liu C-T, Hivert M-F, Strawbridge RJ, Podmore C, Li M, Yao J, Sim X, Hong J, et al (2017). Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis. PLoS Med, 14(9).

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. METHODS & FINDINGS: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

Abstract. Author URL.

Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, et al (2017). Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet, 49(1), 17-26. Abstract. Author URL.

Zillikens MC, Demissie S, Hsu Y-H, Yerges-Armstrong LM, Chou W-C, Stolk L, Livshits G, Broer L, Johnson T, Koller DL, et al (2017). Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun, 8(1). Abstract. Author URL.

Watson RA, Gates AS, Wynn EH, Calvert FE, Girousse A, Lelliott CJ, Barroso I (2017). Lyplal1 is dispensable for normal fat deposition in mice. Dis Model Mech, 10(12), 1481-1488. Abstract. Author URL.

Varga TV, Kurbasic A, Aine M, Eriksson P, Ali A, Hindy G, Gustafsson S, Luan J, Shungin D, Chen Y, et al (2017). Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults. Int J Epidemiol, 46(4), 1211-1222. Abstract. Author URL.

Hendricks AE, Bochukova EG, Marenne G, Keogh JM, Atanassova N, Bounds R, Wheeler E, Mistry V, Henning E, Körner A, et al (2017). Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity. Scientific Reports, 7(1). Abstract.

Flannick J, Fuchsberger C, Mahajan A, Teslovich TM, Agarwala V, Gaulton KJ, Caulkins L, Koesterer R, Ma C, Moutsianas L, et al (2017). Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data, 4 Abstract. Author URL.

Rocha N, Payne F, Huang-Doran I, Sleigh A, Fawcett K, Adams C, Stears A, Saudek V, O'Rahilly S, Barroso I, et al (2017). The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion. Sci Rep, 7(1). Abstract. Author URL.

Tachmazidou I, Süveges D, Min JL, Ritchie GRS, Steinberg J, Walter K, Iotchkova V, Schwartzentruber J, Huang J, Memari Y, et al (2017). Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. Am J Hum Genet, 100(6), 865-884. Abstract. Author URL.

Sallah N, Carstensen T, Wakeham K, Bagni R, Labo N, Pollard MO, Gurdasani D, Ekoru K, Pomilla C, Young EH, et al (2017). Whole-genome association study of antibody response to Epstein-Barr virus in an African population: a pilot. Glob Health Epidemiol Genom, 2 Abstract. Author URL.

Scott RA, Freitag DF, Li L, Chu AY, Surendran P, Young R, Grarup N, Stancáková A, Chen Y, Varga TV, et al (2016). A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Sci Transl Med, 8(341). Abstract. Author URL.

Lotta LA, Sharp SJ, Burgess S, Perry JRB, Stewart ID, Willems SM, Luan J, Ardanaz E, Arriola L, Balkau B, et al (2016). Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: a Meta-analysis. JAMA, 316(13), 1383-1391. Abstract. Author URL.

Ali A, Varga TV, Stojkovic IA, Schulz C-A, Hallmans G, Barroso I, Poveda A, Renström F, Orho-Melander M, Franks PW, et al (2016). Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings from the GLACIER and the MDC Studies. Circ Cardiovasc Genet, 9(2), 162-171.

BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability. METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmö Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4×10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6×10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG×BMI interaction effect (Pinteraction=6.0×10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5×10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG×BMI×sex) was observed (Pinteraction=0.03), where the WGRSTG×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci. CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.

Abstract. Author URL.

Auffray C, Balling R, Barroso I, Bencze L, Benson M, Bergeron J, Bernal-Delgado E, Blomberg N, Bock C, Conesa A, et al (2016). Erratum to: Making sense of big data in health research: towards an EU action plan. Genome Med, 8(1). Author URL.

Ahmad S, Poveda A, Shungin D, Barroso I, Hallmans G, Renström F, Franks PW (2016). Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study. Int J Obes (Lond), 40(9), 1346-1352. Abstract. Author URL.

Robinson PC, Leo PJ, Pointon JJ, Harris J, Cremin K, Bradbury LA, Stebbings S, Harrison AA, Duncan EL, Evans DM, et al (2016). Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease. NPJ GENOMIC MEDICINE, 3 Author URL.

Lotta LA, Scott RA, Sharp SJ, Burgess S, Luan J, Tillin T, Schmidt AF, Imamura F, Stewart ID, Perry JRB, et al (2016). Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: a Mendelian Randomisation Analysis. PLoS Med, 13(11).

BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e. isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. CONCLUSIONS: Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

Abstract. Author URL.

Kilpeläinen TO, Carli JFM, Skowronski AA, Sun Q, Kriebel J, Feitosa MF, Hedman ÅK, Drong AW, Hayes JE, Zhao J, et al (2016). Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels. Nat Commun, 7 Abstract. Author URL.

Poveda A, Koivula RW, Ahmad S, Barroso I, Hallmans G, Johansson I, Renström F, Franks PW (2016). Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study. Diabetologia, 59(3), 462-471. Abstract. Author URL.

Huang-Doran I, Tomlinson P, Payne F, Gast A, Sleigh A, Bottomley W, Harris J, Daly A, Rocha N, Rudge S, et al (2016). Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations. JCI Insight, 1(17). Abstract. Author URL.

Auffray C, Balling R, Barroso I, Bencze L, Benson M, Bergeron J, Bernal-Delgado E, Blomberg N, Bock C, Conesa A, et al (2016). Making sense of big data in health research: Towards an EU action plan. Genome Med, 8(1). Abstract. Author URL.

Majithia AR, Tsuda B, Agostini M, Gnanapradeepan K, Rice R, Peloso G, Patel KA, Zhang X, Broekema MF, Patterson N, et al (2016). Prospective functional classification of all possible missense variants in PPARG. Nat Genet, 48(12), 1570-1575. Abstract. Author URL.

Brunkwall L, Chen Y, Hindy G, Rukh G, Ericson U, Barroso I, Johansson I, Franks PW, Orho-Melander M, Renström F, et al (2016). Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts. Am J Clin Nutr, 104(3), 809-815.

BACKGROUND: the consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain. OBJECTIVE: Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large Swedish cohorts. DESIGN: Data were available for 21,824 healthy participants from the Malmö Diet and Cancer study and 4902 healthy participants from the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study. Self-reported SSB intake was categorized into 4 levels (seldom, low, medium, and high). Unweighted and weighted genetic risk scores (GRSs) were constructed based on 30 body mass index [(BMI) in kg/m(2)]-associated loci, and effect modification was assessed in linear regression equations by modeling the product and marginal effects of the GRS and SSB intake adjusted for age-, sex-, and cohort-specific covariates, with BMI as the outcome. In a secondary analysis, models were additionally adjusted for putative confounders (total energy intake, alcohol consumption, smoking status, and physical activity). RESULTS: in an inverse variance-weighted fixed-effects meta-analysis, each SSB intake category increment was associated with a 0.18 higher BMI (SE = 0.02; P = 1.7 × 10(-20); n = 26,726). In the fully adjusted model, a nominal significant interaction between SSB intake category and the unweighted GRS was observed (P-interaction = 0.03). Comparing the participants within the top and bottom quartiles of the GRS to each increment in SSB intake was associated with 0.24 (SE = 0.04; P = 2.9 × 10(-8); n = 6766) and 0.15 (SE = 0.04; P = 1.3 × 10(-4); n = 6835) higher BMIs, respectively. CONCLUSIONS: the interaction observed in the Swedish cohorts is similar in magnitude to the previous analysis in US cohorts and indicates that the relation of SSB intake and BMI is stronger in people genetically predisposed to obesity.

Abstract. Author URL.

Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, et al (2016). The genetic architecture of type 2 diabetes. Nature, 536(7614), 41-47. Abstract. Author URL.

Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, Thorleifsson G, Luan J, Donnelly LA, Kanoni S, et al (2016). The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet, 48(10), 1171-1184. Abstract. Author URL.

Asimit JL, Panoutsopoulou K, Wheeler E, Berndt SI, GIANT consortium, the arcOGEN consortium, Cordell HJ, Morris AP, Zeggini E, Barroso I (2015). A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits. Genet Epidemiol, 39(8), 624-634. Abstract. Author URL.

Geihs M, Yan Y, Walter K, Huang J, Memari Y, Min JL, Mead D, Hubbard TJ, Timpson NJ, Down TA, et al (2015). An interactive genome browser of association results from the UK10K cohorts project. BIOINFORMATICS, 31(24), 4029-4031. Author URL.

Kozusko K, Tsang V, Bottomley W, Cho YH, Gandotra S, Mimmack ML, Lim K, Isaac I, Patel S, Saudek V, et al (2015). Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy. Diabetes, 64(1), 299-310. Abstract. Author URL.

Roberts CH, Franklin CS, Makalo P, Joof H, Sarr I, Mahdi OS, Sillah A, Bah M, Payne F, Jeffreys AE, et al (2015). Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study. Sci Rep, 5 Abstract. Author URL.

Nettleton JA, Follis JL, Ngwa JS, Smith CE, Ahmad S, Tanaka T, Wojczynski MK, Voortman T, Lemaitre RN, Kristiansson K, et al (2015). Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry. Hum Mol Genet, 24(16), 4728-4738. Abstract. Author URL.

Gaulton KJ, Ferreira T, Lee Y, Raimondo A, Mägi R, Reschen ME, Mahajan A, Locke A, Rayner NW, Robertson N, et al (2015). Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nature Genetics, 47(12), 1415-1425. Abstract.

Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, et al (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206. Abstract. Author URL.

Coffee and Caffeine Genetics Consortium, Cornelis MC, Byrne EM, Esko T, Nalls MA, Ganna A, Paynter N, Monda KL, Amin N, Fischer K, et al (2015). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry, 20(5), 647-656. Abstract. Author URL.

Kaiser VB, Svinti V, Prendergast JG, Chau YY, Campbell A, Patarcic I, Barroso I, Joshi PK, Hastie ND, Miljkovic A, et al (2015). Homozygous loss-of-function variants in European cosmopolitan and isolate populations. Human Molecular Genetics, 24(19), 5464-5474. Abstract.

Mahajan A, Sim X, Ng HJ, Manning A, Rivas MA, Highland HM, Locke AE, Grarup N, Im HK, Cingolani P, et al (2015). Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus. PLoS Genetics, 11(1). Abstract.

Huang J, Howie B, McCarthy S, Memari Y, Walter K, Min JL, Danecek P, Malerba G, Trabetti E, Zheng HF, et al (2015). Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nature Communications, 6 Abstract.

Wessel J, Chu AY, Willems SM, Wang S, Yaghootkar H, Brody JA, Dauriz M, Hivert M-F, Raghavan S, Lipovich L, et al (2015). Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun, 6 Abstract. Author URL.

Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Locke AE, Mägi R, Strawbridge RJ, Pers TH, Fischer K, Justice AE, et al (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196. Abstract. Author URL.

Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Artigas MS, Billington CK, Kheirallah AK, Allen R, Cook JP, et al (2015). Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank. The Lancet Respiratory Medicine, 3(10), 769-781. Abstract.

Lunetta KL, Day FR, Sulem P, Ruth KS, Tung JY, Hinds DA, Esko T, Elks CE, Altmaier E, He C, et al (2015). Rare coding variants and X-linked loci associated with age at menarche. Nat Commun, 6 Abstract. Author URL.

Schmidts M, Hou Y, Cortés CR, Mans DA, Huber C, Boldt K, Patel M, Van Reeuwijk J, Plaza JM, Van Beersum SEC, et al (2015). TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nature Communications, 6 Abstract.

Winkler TW, Justice AE, Graff M, Barata L, Feitosa MF, Chu S, Czajkowski J, Esko T, Fall T, Kilpeläinen TO, et al (2015). The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: a Large-Scale Genome-Wide Interaction Study. PLOS Genetics, 11(10), e1005378-e1005378.

Bielczyk-Maczyńska E, Lam Hung L, Ferreira L, Fleischmann T, Weis F, Fernández-Pevida A, Harvey SA, Wali N, Warren AJ, Barroso I, et al (2015). The Ribosome Biogenesis Protein Nol9 is Essential for Definitive Hematopoiesis and Pancreas Morphogenesis in Zebrafish. PLoS Genet, 11(12). Abstract. Author URL.

Walter K, Min JL, Huang J, Crooks L, Memari Y, McCarthy S, Perry JRB, Xu C, Futema M, Lawson D, et al (2015). The UK10K project identifies rare variants in health and disease. Nature, 526(7571), 82-89. Abstract.

Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, et al (2015). Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat Genet, 47(11), 1282-1293. Abstract. Author URL.

Chen J-H, Segni M, Payne F, Huang-Doran I, Sleigh A, Adams C, UK10K Consortium, Savage DB, O'Rahilly S, Semple RK, et al (2015). Truncation of POC1A associated with short stature and extreme insulin resistance. J Mol Endocrinol, 55(2), 147-158. Abstract. Author URL.

Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ, Mullin BH, Shihab HA, Min J, Walter K, et al (2015). Whole-genome sequence-based analysis of thyroid function. Nature Communications, 6 Abstract.

Psychosis Endophenotypes International Consortium, Wellcome Trust Case-Control Consortium 2, Bramon E, Pirinen M, Strange A, Lin K, Freeman C, Bellenguez C, Su Z, Band G, et al (2014). A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation. Biol Psychiatry, 75(5), 386-397. Abstract. Author URL.

Timpson NJ, Walter K, Min JL, Tachmazidou I, Malerba G, Shin SY, Chen L, Futema M, Southam L, Iotchkova V, et al (2014). A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nature Communications, 5 Abstract.

Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, et al (2014). Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes, 63(12), 4378-4387. Abstract. Author URL.

Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chu AY, Estrada K, Luan J, Kutalik Z, et al (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics, 46(11), 1173-1186. Abstract.

Pearce LR, Joe R, Doche ME, Su H-W, Keogh JM, Henning E, Argetsinger LS, Bochukova EG, Cline JM, Garg S, et al (2014). Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1. Endocrinology, 155(9), 3219-3226. Abstract. Author URL.

Kurbasic A, Poveda A, Chen Y, Agren A, Engberg E, Hu FB, Johansson I, Barroso I, Brändström A, Hallmans G, et al (2014). Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies. Curr Nutr Rep, 3(4), 400-411. Abstract. Author URL.

Langenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, Forouhi NG, Froguel P, Groop LC, Hansen T, Palla L, et al (2014). Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. PLoS Med, 11(5).

BACKGROUND: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS: the InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50×10-3) and waist circumference (p for interaction = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS: the relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Abstract. Author URL.

Varga TV, Sonestedt E, Shungin D, Koivula RW, Hallmans G, Escher SA, Barroso I, Nilsson P, Melander O, Orho-Melander M, et al (2014). Genetic determinants of long-term changes in blood lipid concentrations: 10-year follow-up of the GLACIER study. PLoS Genet, 10(6). Abstract. Author URL.

Florez JC, Barroso I (2014). Genome-wide association studies of glycaemic traits: a MAGICal journey. Frontiers in Diabetes, 23, 42-57. Abstract.

Mahajan A, Go MJ, Zhang W, Below JE, Gaulton KJ, Ferreira T, Horikoshi M, Johnson AD, Ng MCY, Prokopenko I, et al (2014). Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. NATURE GENETICS, 46(3), 234-+. Author URL.

Payne F, Colnaghi R, Rocha N, Seth A, Harris J, Carpenter G, Bottomley WE, Wheeler E, Wong S, Saudek V, et al (2014). Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance. J Clin Invest, 124(9), 4028-4038. Abstract. Author URL.

Dimas AS, Lagou V, Barker A, Knowles JW, Mägi R, Hivert M-F, Benazzo A, Rybin D, Jackson AU, Stringham HM, et al (2014). Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes, 63(6), 2158-2171. Abstract. Author URL.

Osborn DPS, Roccasecca RM, McMurray F, Hernandez-Hernandez V, Mukherjee S, Barroso I, Stemple D, Cox R, Beales PL, Christou-Savina S, et al (2014). Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies. PLoS One, 9(2). Abstract. Author URL.

Payne F, Lim K, Girousse A, Brown RJ, Kory N, Robbins A, Xue Y, Sleigh A, Cochran E, Adams C, et al (2014). Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. Proc Natl Acad Sci U S A, 111(24), 8901-8906. Abstract. Author URL.

Winkler TW, Day FR, Croteau-Chonka DC, Wood AR, Locke AE, Mägi R, Ferreira T, Fall T, Graff M, Justice AE, et al (2014). Quality control and conduct of genome-wide association meta-analyses. Nat Protoc, 9(5), 1192-1212. Abstract. Author URL.

Davis OSP, Band G, Pirinen M, Haworth CMA, Meaburn EL, Kovas Y, Harlaar N, Docherty SJ, Hanscombe KB, Trzaskowski M, et al (2014). The correlation between reading and mathematics ability at age twelve has a substantial genetic component. Nat Commun, 5 Abstract. Author URL.

Semple R, Barroso I (2014). Whole-exome sequencing of patients with severe disorders of insulin action. Frontiers in Diabetes, 23, 87-101. Abstract.

Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, et al (2013). Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature Genetics, 45(11), 1345-1353. Abstract.

Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, et al (2013). Discovery and refinement of loci associated with lipid levels. Nature Genetics, 45(11), 1274-1285. Abstract.

Wheeler E, Huang N, Bochukova EG, Keogh JM, Lindsay S, Garg S, Henning E, Blackburn H, Loos RJF, Wareham NJ, et al (2013). Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. Nat Genet, 45(5), 513-517. Abstract. Author URL.

Ripke S, O'Dushlaine C, Chambert K, Moran JL, Kähler AK, Akterin S, Bergen SE, Collins AL, Crowley JJ, Fromer M, et al (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet, 45(10), 1150-1159. Abstract. Author URL.

Donnelly P, Strange A, Bellenguez C, Sim X, Luben R, Hysi PG, Ramdas WD, van Koolwijk LME, Freeman C, Pirinen M, et al (2013). Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus. HUMAN MOLECULAR GENETICS, 22(22), 4653-4660. Author URL.

Berndt SI, Gustafsson S, Mägi R, Ganna A, Wheeler E, Feitosa MF, Justice AE, Monda KL, Croteau-Chonka DC, Day FR, et al (2013). Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nature Genetics

Tanaka T, Ngwa JS, van Rooij FJA, Zillikens MC, Wojczynski MK, Frazier-Wood AC, Houston DK, Kanoni S, Lemaitre RN, Luan J, et al (2013). Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. Am J Clin Nutr, 97(6), 1395-1402.

BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: the objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: a variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10(-10)), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Abstract. Author URL.

Doche ME, Bochukova EG, Su H-W, Pearce LR, Keogh JM, Henning E, Cline JM, Saeed S, Dale A, Cheetham T, et al (2013). Human SH2B1 mutations are associated with maladaptive behaviors and obesity (vol 123, pg 526, 2013). JOURNAL OF CLINICAL INVESTIGATION, 123(1), 526-526. Author URL.

Choong E, Quteineh L, Cardinaux J-R, Gholam-Rezaee M, Vandenberghe F, Dobrinas M, Bondolfi G, Etter M, Holzer L, Magistretti P, et al (2013). Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population. JAMA PSYCHIATRY, 70(10), 1011-1019. Author URL.

Pearce LR, Atanassova N, Banton MC, Bottomley B, van der Klaauw AA, Revelli J-P, Hendricks A, Keogh JM, Henning E, Doree D, et al (2013). KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Cell, 155(4), 765-777. Abstract. Author URL.

CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, et al (2013). Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet, 45(1), 25-33. Abstract. Author URL.

Huertas-Vazquez A, Nelson CP, Guo X, Reinier K, Uy-Evanado A, Teodorescu C, Ayala J, Jerger K, Chugh H, WTCCC+, et al (2013). Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease. PLoS One, 8(4). Abstract. Author URL.

Ramachandrappa S, Raimondo A, Cali AMG, Keogh JM, Henning E, Saeed S, Thompson A, Garg S, Bochukova EG, Brage S, et al (2013). Rare variants in single-minded 1 (SIM1) are associated with severe obesity. Journal of Clinical Investigation, 123(7), 3042-3050. Abstract.

(2013). Rare variants in single-minded 1 (SIM1) are associated with severe obesity. The Journal of clinical investigation, 123(8), 3635-3635.

Ramachandrappa S, Raimondo A, Cali AMG, Keogh JM, Henning E, Saeed S, Thompson A, Garg S, Bochukova EG, Brage S, et al (2013). Rare variants in single-minded 1 (SIM1) are associated with severe obesity (vol 123, pg 3042, 2013). JOURNAL OF CLINICAL INVESTIGATION, 123(8), 3635-3635. Author URL.

Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, Monda KL, Kilpeläinen TO, Esko T, Mägi R, Li S, et al (2013). Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits. PLoS Genetics, 9(6). Abstract.

Prudente S, Copetti M, Morini E, Mendonca C, Andreozzi F, Chandalia M, Baratta R, DIAGRAM consortium, Pellegrini F, Mercuri L, et al (2013). The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry. Nutr Metab Cardiovasc Dis, 23(11), 1043-1049. Abstract. Author URL.

Seth A, Stemple DL, Barroso I (2013). The emerging use of zebrafish to model metabolic disease. Dis Model Mech, 6(5), 1080-1088. Abstract. Author URL.

InterAct Consortium, Scott RA, Langenberg C, Sharp SJ, Franks PW, Rolandsson O, Drogan D, van der Schouw YT, Ekelund U, Kerrison ND, et al (2013). The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study. Diabetologia, 56(1), 60-69. Abstract. Author URL.

Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I, et al (2012). A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nature Genetics, 44(6), 659-669. Abstract.

Manning AK, Hivert M-F, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu C-T, Bielak LF, Prokopenko I, et al (2012). A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nature Genetics

Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, Hypponen E, Holst C, Valcarcel B, Thiering E, et al (2012). A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics

Palmer ND, McDonough CW, Hicks PJ, Roh BH, Wing MR, an SS, Hester JM, Cooke JN, Bostrom MA, Rudock ME, et al (2012). A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One, 7(1). Abstract. Author URL.

Boraska V, Jerončić A, Colonna V, Southam L, Nyholt DR, William rayner N, Perry JRB, Toniolo D, Albrecht E, Ang W, et al (2012). Genome-wide meta-analysis of common variant differences between men and women. Human Molecular Genetics, 21(21), 4805-4815. Abstract.

Doche ME, Bochukova EG, Su H-W, Pearce LR, Keogh JM, Henning E, Cline JM, Saeed S, Dale A, Cheetham T, et al (2012). Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest, 122(12), 4732-4736. Abstract. Author URL.

Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, MäGi R, Strawbridge RJ, Rehnberg E, Gustafsson S, et al (2012). Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics, 44(9), 991-1005. Abstract.

Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, Mägi R, Strawbridge RJ, Rehnberg E, Gustafsson S, et al (2012). Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics

Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A, et al (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. NATURE GENETICS, 44(9), 981-+. Author URL.

Morris AP, Ferreira T, Mahajan A, Prokopenko I, Kumar A, Lagou V, Lindgren CM, Rayner NW, Wiltshire S, Dimas AS, et al (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-990. Abstract.

Lindhurst MJ, Parker VER, Payne F, Sapp JC, Rudge S, Harris J, Witkowski AM, Zhang Q, Groeneveld MP, Scott CE, et al (2012). Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet, 44(8), 928-933. Abstract. Author URL.

Scott RA, Chu AY, Grarup N, Manning AK, Hivert M-F, Shungin D, Toenjes A, Yesupriya A, Barnes D, Bouatia-Naji N, et al (2012). No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels. DIABETES, 61(5), 1291-1296. Author URL.

Barroso I (2012). Non-coding but functional. NATURE, 489(7414), 54-54. Author URL.

Dastani Z, Hivert MF, Timpson NJ, Perry JRB, Yuan X, Scott RA, Henneman P, Heid IM, Kizer JR, Lyytikäinen LP, et al (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genetics, 8(3). Abstract.

Bonnefond A, Clément N, Fawcett K, Yengo L, Vaillant E, Guillaume J-L, Dechaume A, Payne F, Roussel R, Czernichow S, et al (2012). Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet, 44(3), 297-301. Abstract. Author URL.

Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, Wallace C, Stevens H, Coleman G, Wellcome Trust Case Control Consortium, et al (2012). Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet, 21(23), 5202-5208. Abstract. Author URL.

Voight BF, Kang HM, Ding J, Palmer CD, Sidore C, Chines PS, Burtt NP, Fuchsberger C, Li Y, Erdmann J, et al (2012). The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits. PLoS Genetics, 8(8). Abstract.

Obeidat M, Wain LV, Shrine N, Kalsheker N, Artigas MS, Repapi E, Burton PR, Johnson T, Ramasamy A, Zhao JH, et al (2011). A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample. PLoS ONE, 6(5). Abstract.

Bown MJ, Jones GT, Harrison SC, Wright BJ, Bumpstead S, Baas AF, Gretarsdottir S, Badger SA, Bradley DT, Burnand K, et al (2011). Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. American Journal of Human Genetics, 89(5), 619-627. Abstract.

Hussain K, Challis B, Rocha N, Payne F, Minic M, Thompson A, Daly A, Scott C, Harris J, Smillie BJL, et al (2011). An activating mutation of AKT2 and human hypoglycemia. Science, 334(6055). Abstract. Author URL.

Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, Bouatia-Naji N, Langenberg C, Prokopenko I, Stolerman E, et al (2011). Common variants at 10 genomic loci influence hemoglobin A<inf>1C</inf> levels via glycemic and nonglycemic pathways (Diabetes (2010) 59, (3229-3239)). Diabetes, 60(3).

InterAct Consortium, Langenberg C, Sharp S, Forouhi NG, Franks PW, Schulze MB, Kerrison N, Ekelund U, Barroso I, Panico S, et al (2011). Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study. Diabetologia, 54(9), 2272-2282.

AIMS/HYPOTHESIS: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. METHODS: Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. RESULTS: a total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. CONCLUSIONS/INTERPRETATION: InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

Abstract. Author URL.

Raffan E, Hurst LA, Turki SA, Carpenter G, Scott C, Daly A, Coffey A, Bhaskar S, Howard E, Khan N, et al (2011). Early Diagnosis of Werner's Syndrome Using Exome-Wide Sequencing in a Single, Atypical Patient. Front Endocrinol (Lausanne), 2 Abstract. Author URL.

Soler Artigas M, Wain LV, Repapi E, Obeidat M, Sayers I, Burton PR, Johnson T, Zhao JH, Albrecht E, Dominiczak AF, et al (2011). Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function. Am J Respir Crit Care Med, 184(7), 786-795. Abstract. Author URL.

Raffan E, Soos MA, Rocha N, Tuthill A, Thomsen AR, Hyden CS, Gregory JW, Hindmarsh P, Dattani M, Cochran E, et al (2011). Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling. Diabetologia, 54(5), 1057-1065. Abstract. Author URL.

Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang S-J, et al (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. NATURE, 478(7367), 103-109. Author URL.

Kilpeläinen TO, Zillikens MC, Stančákova A, Finucane FM, Ried JS, Langenberg C, Zhang W, Beckmann JS, Luan J, Vandenput L, et al (2011). Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nature Genetics, 43(8), 753-760. Abstract.

Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist E, Rybin D, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, et al (2011). Genome-Wide Association Identifies Nine Common Variants Associated with Fasting Proinsulin Levels and Provides New Insights into the Pathophysiology of Type 2 Diabetes. DIABETES, 60(10), 2624-2634. Author URL.

Artigas MS, Loth DW, Wain LV, Gharib SA, Obeidat M, Tang W, Zhai G, Zhao JH, Smith AV, Huffman JE, et al (2011). Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nature Genetics, 43(11), 1082-1090. Abstract.

Wheeler E, Barroso I (2011). Genome-wide association studies and type 2 diabetes. Brief Funct Genomics, 10(2), 52-60. Abstract. Author URL.

Wain LV, Verwoert GC, O'reilly PF, Shi G, Johnson T, Johnson AD, Bochud M, Rice KM, Henneman P, Smith AV, et al (2011). Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nature Genetics, 43(10), 1005-1012. Abstract.

Pfister R, Sharp S, Luben R, Welsh P, Barroso I, Salomaa V, Meirhaeghe A, Khaw K-T, Sattar N, Langenberg C, et al (2011). Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies. PLoS Med, 8(10).

BACKGROUND: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. METHODS AND FINDINGS: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. CONCLUSIONS: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary.

Abstract. Author URL.

Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Maegi R, et al (2011). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. NATURE GENETICS, 43(11), 1164-1164. Author URL.

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Nica AC, Parts L, Glass D, Nisbet J, Barrett A, Sekowska M, Travers M, Potter S, Grundberg E, Small K, et al (2011). The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet, 7(2). Abstract. Author URL.

Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, et al (2011). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis (vol 42, pg 579, 2010). NATURE GENETICS, 43(4), 388-388. Author URL.

Dash S, Langenberg C, Fawcett KA, Semple RK, Romeo S, Sharp S, Sano H, Lienhard GE, Rochford JJ, Howlett T, et al (2010). Analysis of TBC1D4 in patients with severe insulin resistance. Diabetologia, 53(6), 1239-1242. Author URL.

Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Allen HL, Lindgren CM, Luan J, Maegi R, et al (2010). Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. NATURE GENETICS, 42(11), 937-U53. Author URL.

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Nica AC, Montgomery SB, Dimas AS, Stranger BE, Beazley C, Barroso I, Dermitzakis ET (2010). Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations. PLoS Genet, 6(4). Abstract. Author URL.

Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, Bouatia-Naji N, Langenberg C, Prokopenko I, Stolerman E, et al (2010). Common variants at 10 genomic loci influence hemoglobin A<inf>1C</inf> levels via glycemic and nonglycemic pathways. Diabetes, 59(12), 3229-3239.

OBJECTIVE - Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA 1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS - We studied associations with HbA 1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS - Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10-26), HFE (rs1800562/P = 2.6 × 10-20), TMPRSS6 (rs855791/P = 2.7 x 10-14), ANK1 (rs4737009/P = 6.1 × 10-12), SPTA1 (rs2779116/P = 2.8 × 10-9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10 -9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10-54), MTNR1B (rs1387153/P = 4.0 × 10-11), GCK (rs1799884/P = 1.5 × 10-20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10-18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA 1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS - GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c. © 2010 by the American Diabetes Association.

Abstract.

Fawcett KA, Wheeler E, Morris AP, Ricketts SL, Hallmans G, Rolandsson O, Daly A, Wasson J, Permutt A, Hattersley AT, et al (2010). Detailed Investigation of the Role of Common and Low-Frequency WFS1 Variants in Type 2 Diabetes Risk. DIABETES, 59(3), 741-746. Author URL.

Ingelsson E, Langenberg C, Hivert M-F, Prokopenko I, Lyssenko V, Dupuis J, Mägi R, Sharp S, Jackson AU, Assimes TL, et al (2010). Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. Diabetes, 59(5), 1266-1275. Abstract. Author URL.

Fontaine-Bisson B, Renström F, Rolandsson O, MAGIC, Payne F, Hallmans G, Barroso I, Franks PW (2010). Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population. Diabetologia, 53(10), 2155-2162.

AIMS/HYPOTHESIS: We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. METHODS: Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. RESULTS: Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 x 10(-6) vs null model), but lower discriminative power than model 1 (p = 5.92 x 10(-5)). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 x 10(-9)) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 x 10(-7) vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 x 10(-20)) and model 1 (p = 1.32 x 10(-5)); its ROC AUC was 0.626. CONCLUSIONS/INTERPRETATION: Adding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci.

Abstract. Author URL.

Perry JRB, Weedon MN, Langenberg C, Jackson AU, Lyssenko V, Sparsø T, Thorleifsson G, Grallert H, Ferrucci L, Maggio M, et al (2010). Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum Mol Genet, 19(3), 535-544. Abstract. Author URL.

Waterworth DM, Ricketts SL, Song K, Chen L, Zhao JH, Ripatti S, Aulchenko YS, Zhang W, Yuan X, Lim N, et al (2010). Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(11), 2264-2276. Abstract.

Saxena R, Hivert M-F, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, Lyssenko V, Bouatia-Naji N, Dupuis J, Jackson AU, et al (2010). Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. NATURE GENETICS, 42(2), 142-U75. Author URL.

Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, et al (2010). Genome-wide association study identifies five loci associated with lung function. Nat Genet, 42(1), 36-44. Abstract. Author URL.

Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, Vukcevic D, Barnes C, Conrad DF, Giannoulatou E, et al (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. NATURE, 464(7289), 713-U86. Author URL.

Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, Vukcevic D, Barnes C, Conrad DF, et al (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature, 464(7289), 713-720. Abstract. Author URL.

Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, et al (2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature, 467(7317), 832-838. Abstract. Author URL.

Kirk J, Porter KM, Parker V, Barroso I, O'Rahilly S, Hendriksz C, Semple RK (2010). Loss of NPC1 function in a patient with a co-inherited novel insulin receptor mutation does not grossly modify the severity of the associated insulin resistance. J Inherit Metab Dis, 33 Suppl 3(Suppl 3), S227-S232. Abstract. Author URL.

Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW, Yuan X, Waeber G, et al (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. NATURE GENETICS, 42(5), 436-U75. Author URL.

Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Maegi R, et al (2010). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. NATURE GENETICS, 42(11), 949-U160. Author URL.

Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, et al (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet, 42(2), 105-116. Abstract. Author URL.

Fawcett KA, Barroso I (2010). The genetics of obesity: FTO leads the way. Trends Genet, 26(6), 266-274. Abstract. Author URL.

Elks CE, Perry JRB, Sulem P, Chasman DI, Franceschini N, He C, Lunetta KL, Visser JA, Byrne EM, Cousminer DL, et al (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. NATURE GENETICS, 42(12), 1077-1U73. Author URL.

Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, et al (2010). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. NATURE GENETICS, 42(7), 579-U155. Author URL.

Dash S, Sano H, Rochford JJ, Semple RK, Yeo G, Hyden CSS, Soos MA, Clark J, Rodin A, Langenberg C, et al (2009). A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia. Proc Natl Acad Sci U S A, 106(23), 9350-9355. Abstract. Author URL.

Langenberg C, Pascoe L, Mari A, Tura A, Laakso M, Frayling TM, Barroso I, Loos RJF, Wareham NJ, Walker M, et al (2009). Common genetic variation in the melatonin receptor 1B gene (MTNR1B) is associated with decreased early-phase insulin response. DIABETOLOGIA, 52(8), 1537-1542. Author URL.

Ong KK, Elks CE, Li S, Zhao JH, Luan J, Andersen LB, Bingham SA, Brage S, Smith GD, Ekelund U, et al (2009). Genetic variation in LIN28B is associated with the timing of puberty. Nat Genet, 41(6), 729-733. Abstract. Author URL.

Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L, Speliotes EK, Thorleifsson G, Willer CJ, Herrera BM, et al (2009). Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution. PLOS GENETICS, 5(6). Author URL.

Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, et al (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics, 41(6), 666-676. Abstract.

Bottomley WE, Soos MA, Adams C, Guran T, Howlett TA, Mackie A, Miell J, Monson JP, Temple R, Tenenbaum-Rakover Y, et al (2009). IRS2 variants and syndromes of severe insulin resistance. Diabetologia, 52(6), 1208-1211. Author URL.

Southam L, Soranzo N, Montgomery SB, Frayling TM, McCarthy MI, Barroso I, Zeggini E (2009). Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants?. DIABETOLOGIA, 52(9), 1846-1851. Author URL.

Soranzo N, Rivadeneira F, Chinappen-Horsley U, Malkina I, Richards JB, Hammond N, Stolk L, Nica A, Inouye M, Hofman A, et al (2009). Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. PLoS Genet, 5(4). Abstract. Author URL.

Rubio-Cabezas O, Puri V, Murano I, Saudek V, Semple RK, Dash S, Hyden CSS, Bottomley W, Vigouroux C, Magré J, et al (2009). Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med, 1(5), 280-287. Abstract. Author URL.

Renström F, Payne F, Nordström A, Brito EC, Rolandsson O, Hallmans G, Barroso I, Nordström P, Franks PW, GIANT Consortium, et al (2009). Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet, 18(8), 1489-1496. Abstract. Author URL.

Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, et al (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet, 41(1), 25-34. Abstract. Author URL.

Salanti G, Southam L, Altshuler D, Ardlie K, Barroso I, Boehnke M, Cornelis MC, Frayling TM, Grallert H, Grarup N, et al (2009). Underlying Genetic Models of Inheritance in Established Type 2 Diabetes Associations. AMERICAN JOURNAL OF EPIDEMIOLOGY, 170(5), 537-545. Author URL.

Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, Loos RJF, Manning AK, Jackson AU, Aulchenko Y, et al (2009). Variants in MTNR1B influence fasting glucose levels. NATURE GENETICS, 41(1), 77-81. Author URL.

Loos RJF, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP, Beckmann JS, et al (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet, 40(6), 768-775. Abstract. Author URL.

Fawcett KA, Grimsey N, Loos RJF, Wheeler E, Daly A, Soos M, Semple R, Syddall H, Cooper C, Siniossoglou S, et al (2008). Evaluating the role of LPIN1 variation in insulin resistance, body weight, and human lipodystrophy in UK populations. DIABETES, 57(9), 2527-2533. Author URL.

Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JRB, Stevens S, Hall AS, et al (2008). Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet, 40(5), 575-583. Abstract. Author URL.

Vimaleswaran KS, Franks PW, Barroso I, Brage S, Ekelund U, Wareham NJ, Loos RJF (2008). Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressure. AMERICAN JOURNAL OF HYPERTENSION, 21(3), 297-302. Author URL.

Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, Song K, Yuan X, Johnson T, Ashford S, et al (2008). LDL-cholesterol concentrations: a genome-wide association study. The Lancet, 371(9611), 483-491.

Background: LDL cholesterol has a causal role in the development of cardiovascular disease. Improved understanding of the biological mechanisms that underlie the metabolism and regulation of LDL cholesterol might help to identify novel therapeutic targets. We therefore did a genome-wide association study of LDL-cholesterol concentrations. Methods: We used genome-wide association data from up to 11 685 participants with measures of circulating LDL-cholesterol concentrations across five studies, including data for 293 461 autosomal single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% or more that passed our quality control criteria. We also used data from a second genome-wide array in up to 4337 participants from three of these five studies, with data for 290 140 SNPs. We did replication studies in two independent populations consisting of up to 4979 participants. Statistical approaches, including meta-analysis and linkage disequilibrium plots, were used to refine association signals; we analysed pooled data from all seven populations to determine the effect of each SNP on variations in circulating LDL-cholesterol concentrations. Findings: in our initial scan, we found two SNPs (rs599839 [p=1·7×10-15] and rs4970834 [p=3·0×10-11]) that showed genome-wide statistical association with LDL cholesterol at chromosomal locus 1p13.3. The second genome screen found a third statistically associated SNP at the same locus (rs646776 [p=4·3×10-9]). Meta-analysis of data from all studies showed an association of SNPs rs599839 (combined p=1·2×10-33) and rs646776 (p=4·8×10-20) with LDL-cholesterol concentrations. SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L. Interpretation: We found evidence for a novel locus for LDL cholesterol on chromosome 1p13.3. These results potentially provide insight into the biological mechanisms that underlie the regulation of LDL cholesterol and might help in the discovery of novel therapeutic targets for cardiovascular disease. © 2008 Elsevier Ltd. All rights reserved.

Abstract.

Sandhu MS, Debenham SL, Barroso I, Loos RJF (2008). Mendelian randomisation studies of type 2 diabetes: future prospects. Diabetologia, 51(2), 211-213. Author URL.

Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, de Bakker PIW, Abecasis GR, Almgren P, Andersen G, et al (2008). Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet, 40(5), 638-645. Abstract. Author URL.

Barroso I, Luan J, Wheeler E, Whittaker P, Wasson J, Zeggini E, Weedon MN, Hunt S, Venkatesh R, Frayling TM, et al (2008). Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies. Diabetes, 57(11), 3161-3165. Abstract. Author URL.

Franks PW, Rolandsson O, Debenham SL, Fawcett KA, Payne F, Dina C, Froguel P, Mohlke KL, Willer C, Olsson T, et al (2008). Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. Diabetologia, 51(3), 458-463. Abstract. Author URL.

Florez JC, Jablonski KA, McAteer J, Sandhu MS, Wareham NJ, Barroso I, Franks PW, Altshuler D, Knowler WC, Diabetes Prevention Program Research Group, et al (2008). Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. Diabetologia, 51(3), 451-457. Abstract. Author URL.

Vimaleswaran KS, Luan J, Andersen G, Muller YL, Wheeler E, Brito EC, O'Rahilly S, Pedersen O, Baier LJ, Knowler WC, et al (2008). The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals. JOURNAL OF APPLIED PHYSIOLOGY, 105(4), 1352-1358. Author URL.

Teo YY, Inouye M, Small KS, Fry AE, Potter SC, Dunstan SJ, Seielstad M, Barroso I, Wareham NJ, Rockett KA, et al (2008). Whole genome-amplified DNA: insights and imputation. NATURE METHODS, 5(4), 279-280. Author URL.

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JRB, Elliott KS, Lango H, Rayner NW, et al (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316(5826), 889-894. Abstract. Author URL.

Collins SC, Luan J, Thompson AJ, Daly A, Semple RK, O'Rahilly S, Wareham NJ, Barroso I (2007). Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations. Diabetologia, 50(3), 555-562. Abstract. Author URL.

Tan K, Kimber WA, Luan J, Soos MA, Semple RK, Wareham NJ, O'Rahilly S, Barroso I (2007). Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypes. DIABETES, 56(3), 714-719. Author URL.

Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, Lank E, Bottomley B, Lopez-Fernandez J, Ferraz-Amaro I, et al (2007). Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. NEW ENGLAND JOURNAL OF MEDICINE, 356(3), 237-247. Author URL.

Loos RJF, Barroso I, O'Rahilly S, Wareham NJ (2007). Comment on "A common genetic variant is associated with adult and childhood obesity". SCIENCE, 315(5809). Author URL.

Sandhu MS, Weedon MN, Fawcett KA, Wasson J, Debenham SL, Daly A, Lango H, Frayling TM, Neumann RJ, Sherva R, et al (2007). Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet, 39(8), 951-953. Abstract. Author URL.

Mesa JL, Loos RJF, Franks PW, Ong KK, Luan J, O'Rahilly S, Wareham NJ, Barroso I (2007). Lamin A/C polymorphisms, type 2 diabetes, and the metabolic syndrome - Case-control and quantitative trait studies. DIABETES, 56(3), 884-889. Author URL.

Franks PW, Ekelund U, Brage S, Luan J, Schafer AJ, O'Rahilly S, Barroso I, Wareham NJ (2007). PPARGC1A coding variation may initiate impaired NEFA clearance during glucose challenge. Diabetologia, 50(3), 569-573. Abstract. Author URL.

Loos RJF, Franks PW, Francis RW, Barroso I, Gribble FM, Savage DB, Ong KK, O'Rahilly S, Wareham NJ (2007). TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British europid population. DIABETES, 56(7), 1943-1947. Author URL.

Young EH, Wareham NJ, Farooqi S, Hinney A, Hebebrand J, Scherag A, O'rahilly S, Barroso I, Sandhu MS (2007). The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. Int J Obes (Lond), 31(9), 1437-1441. Abstract. Author URL.

Gerken T, Girard CA, Tung Y-CL, Webby CJ, Saudek V, Hewitson KS, Yeo GSH, McDonough MA, Cunliffe S, McNeill LA, et al (2007). The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. SCIENCE, 318(5855), 1469-1472. Author URL.

Barroso I, Luan J, Sandhu MS, Franks PW, Crowley V, Schafer AJ, O'Rahilly S, Wareham NJ (2006). Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes. Diabetologia, 49(3), 501-505. Abstract. Author URL.

Agostini M, Schoenmakers E, Mitchell C, Szatmari I, Savage D, Smith A, Rajanayagam O, Semple R, Luan J, Bath L, et al (2006). Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance. Cell Metab, 4(4), 303-311. Abstract. Author URL.

Fawcett KA, Wareham NJ, Luan J, Syddall H, Cooper C, O'Rahilly S, Day INM, Sandhu MS, Barroso I (2006). PARL Leu262Val is not associated with fasting insulin levels in UK populations. Diabetologia, 49(11), 2649-2652. Abstract. Author URL.

Harding A-H, Loos RJF, Luan J, O'Rahilly S, Wareham NJ, Barroso I (2006). Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes. Diabetologia, 49(11), 2642-2648. Abstract. Author URL.

Barroso I (2005). Complex disease: pleiotropic gene effects in obesity and type 2 diabetes. Eur J Hum Genet, 13(12), 1243-1244. Author URL.

Watiker V, Lachman RS, Wilcox WR, Barroso I, Schafer AJ, Scherer G (2005). Differentiating campomelic dysplasia from Cumming syndrome. Am J Med Genet A, 135(1), 110-112. Author URL.

O'Rahilly S, Barroso I, Wareham NJ (2005). Genetic factors in type 2 diabetes: the end of the beginning?. Science, 307(5708), 370-373. Abstract. Author URL.

Barroso I (2005). Genetics of Type 2 diabetes. Diabet Med, 22(5), 517-535. Abstract. Author URL.

Lucia A, Gómez-Gallego F, Barroso I, Rabadán M, Bandrés F, San Juan AF, Chicharro JL, Ekelund U, Brage S, Earnest CP, et al (2005). PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men. J Appl Physiol (1985), 99(1), 344-348. Abstract. Author URL.

Franks PW, Luan J, Barroso I, Brage S, Gonzalez Sanchez JL, Ekelund U, Ríos MS, Schafer AJ, O'Rahilly S, Wareham NJ, et al (2005). Variation in the eNOS gene modifies the association between total energy expenditure and glucose intolerance. Diabetes, 54(9), 2795-2801. Abstract. Author URL.

George S, Rochford JJ, Wolfrum C, Gray SL, Schinner S, Wilson JC, Soos MA, Murgatroyd PR, Williams RM, Acerini CL, et al (2004). A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science, 304(5675), 1325-1328. Abstract. Author URL.

Savage DB, Soos MA, Powlson A, O'Rahilly S, McFarlane I, Halsall DJ, Barroso I, Thomas EL, Bell JD, Scobie I, et al (2004). Familial partial lipodystrophy associated with compound heterozygosity for novel mutations in the LMNA gene. Diabetologia, 47(4), 753-756. Author URL.

Laudes M, Barroso I, Luan J, Soos MA, Yeo G, Meirhaeghe A, Logie L, Vidal-Puig A, Schafer AJ, Wareham NJ, et al (2004). Genetic variants in human sterol regulatory element binding protein-1c in syndromes of severe insulin resistance and type 2 diabetes. Diabetes, 53(3), 842-846. Abstract. Author URL.

Barroso I, Luan J, Middelberg RPS, Harding A-H, Franks PW, Jakes RW, Clayton D, Schafer AJ, O'Rahilly S, Wareham NJ, et al (2003). Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol, 1(1). Abstract. Author URL.

Franks PW, Barroso I, Luan J, Ekelund U, Crowley VEF, Brage S, Sandhu MS, Jakes RW, Middelberg RPS, Harding A-H, et al (2003). PGC-1alpha genotype modifies the association of volitional energy expenditure with [OV0312]O2max. Med Sci Sports Exerc, 35(12), 1998-2004.

UNLABELLED: Sedentary lifestyles are increasingly common and result in low cardiorespiratory fitness ([OV0312]O2max), a well-established predictor of early mortality and coronary heart disease (CHD). Adaptation in [OV0312]O2max after exercise training varies considerably between people. Because there are hereditary components to fitness, it is likely that genetic factors explain some of this variability. PPARGC1 (PGC-1alpha) coactivates genes involved in energy transduction and mitochondrial biogenesis. Transgenic mouse data demonstrate that overexpression of PGC-1alpha mRNA increases endurance capacity by transformation of nonoxidative to oxidative skeletal muscle tissue. Other murine studies demonstrate that exercise increases PGC-1alpha mRNA expression. PURPOSE: to explore whether a candidate polymorphism in the PGC-1alpha gene modifies the association between physical activity energy expenditure (PAEE) and predicted [OV0312]O2max ([OV0312]O2max.pred). METHOD: We examined whether the Gly482Ser polymorphism of PGC-1alpha modified the relationship between objectively measured PAEE and [OV0312]O2max.pred in a population-based sample of 599 healthy middle-aged people. PAEE was assessed using individual calibration with 4 d of heart rate monitoring. [OV0312]O2max.pred was measured during a submaximal exercise stress test on a bicycle ergometer. RESULTS: Homozygosity at the Ser482 allele was found in 12.7% of the cohort, whereas 38.9% and 48.4% carried the Gly482Gly and Gly482Ser genotypes, respectively. The association between PAEE and [OV0312]O2max.pred (mL x kg(-1) x min(-1)) was strongest in people homozygous for the Ser482 allele (beta = 12.03; P < 0.00001) compared with carriers of the Gly allele (beta = 5.61; P < 0.00001). In a recessive model for the Ser482 allele, the interaction between PAEE and genotype on [OV0312]O2max.pred (L x min(-1)) was highly significant (P = 0.009). CONCLUSION: Our results indicate that Ser482 homozygotes may be most capable of improving cardiorespiratory fitness when physically active, and that Gly482Ser may explain some of the between-person variance previously reported in cardiorespiratory adaptation after exercise training.

Abstract. Author URL.

Savage DB, Agostini M, Barroso I, Gurnell M, Luan J, Meirhaeghe A, Harding A-H, Ihrke G, Rajanayagam O, Soos MA, et al (2002). Digenic inheritance of severe insulin resistance in a human pedigree. Nat Genet, 31(4), 379-384. Abstract. Author URL.

Berger D, Barroso I, Soos M, Yeo G, Schafer AJ, O'Rahilly S, Whitehead JP (2002). Genetic variants of insulin receptor substrate-1 (IRS-1) in syndromes of severe insulin resistance. Functional analysis of Ala513Pro and Gly1158Glu IRS-1. Diabet Med, 19(10), 804-809. Abstract. Author URL.

Preiss S, Argentaro A, Clayton A, John A, Jans DA, Ogata T, Nagai T, Barroso I, Schafer AJ, Harley VR, et al (2001). Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation. J Biol Chem, 276(30), 27864-27872. Abstract. Author URL.

Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen GL, Williams TD, Lewis H, Schafer AJ, et al (1999). Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature, 402(6764), 880-883. Abstract. Author URL.

Richards FM, Goudie DR, Cooper WN, Jene Q, Barroso I, Wicking C, Wainwright BJ, Ferguson-Smith MA (1997). Mapping the multiple self-healing squamous epithelioma (MSSE) gene and investigation of xeroderma pigmentosum group a (XPA) and PATCHED (PTCH) as candidate genes. Hum Genet, 101(3), 317-322. Abstract. Author URL.

Chapters

Barroso I, Scott R (2016). Genome-wide association studies of quantitative glycaemic traits. In (Ed) The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation, 63-89. Abstract.

Stevenson C, Barroso I, Wareham N (2006). The Genetics of Type 2 Diabetes. In (Ed) Nutritional Genomics: Impact on Health and Disease, 222-265.

Conferences

Hernandez NJ, Soenksen J, Newcombe P, Sandhu M, Barroso I, Wallace C, Asimit J (2022). A Flexible and Shared Information Fine-mapping Approach with an application to 33 cardiometabolic traits from a Ugandan cohort. Author URL.

Soenksen J, Chen J, Asimit JL, Magic, Barroso I (2021). Leveraging Information across Multiple Related Glycaemic Traits Improves Fine-Mapping Resolution. Author URL.

Moore R, Barroso I, Stegle O (2018). Exploring genotype-environment (G x E) interactions phenome-wide. Author URL.

Aguilera FR-M, Oliver-Williams C, Karthikeyan S, Walters K, Kundu K, Danesh J, Wheeler E, Zeggini E, Butterworth A, Barroso I, et al (2018). Next-generation sequencing aligned to high-resolution Nuclear Magnetic Resonance (NMR) measurements reveal role of rare variation in circulating metabolic biomarkers. Author URL.

Adeyemo AA, Sun M, Chen J, Wheeler E, Mahajan A, Pirie F, Doumatey A, Sandhu M, Morris A, Motala A, et al (2017). A Meta-analysis of Genome-Wide Association Studies for Type 2 Diabetes in Africans. Author URL.

Hendricks AE, Billups S, Zeggini E, Barroso I, Santorico SA, Dupuis J (2016). A New Method for Genetic Region Association Testing with Massively Different Sequencing Depths of Coverage. Author URL.

Leong A, Wheeler E, Hivert M-F, Liu C-T, Dupuis J, Tai ES, Rotter JI, Florez JC, Barroso I, Meigs JB, et al (2016). Erythrocytic Genetic Variants that Raise Hemoglobin A1c Independently of Glycemia Are Associated with Coronary Artery Disease. Author URL.

Sallah N, Carstensen T, Wakeham K, Bagni R, Labo N, Pollard MO, Gurdasani D, Ekoru K, Fatumo S, Pomilla C, et al (2016). Novel Genome-Wide Sequence Variants Influence Antibody Response to Epstein-Barr Virus in an African Population. Author URL.

Moore R, Casale FP, Barroso I, Stegle O (2016). TreeLMM: Modelling Heterogeneity of Genetic Effects. Author URL.

Justice A, North K, Loos R, Vedantam S, Day F, Berndt S, Gustafsson S, Locke A, Powell C, Bratati K, et al (2013). Meta-analysis of Genetic Associations in up to 339,224 Individuals Identify 66 New Loci for Bmi, Confirming a Neuronal Contribution to Body Weight Regulation and Implicating Several Novel Pathways. Author URL.

Dimas AS, Gomes VI, Knowles J, Maegi R, Barker A, Hivert M-F, Benazzo A, Rybin D, Assimes TI, Ouertermous T, et al (2012). Impact of Type 2 Diabetes Susceptibility Loci on Variation in Physiologic Glycaemic Traits in Non-Diabetic Individuals. Author URL.

Shungin D, Ferreira T, Croteau-Chonka DC, Winkler TW, Magi R, Wu J, Strawbridge RJ, Locke AE, Fischer K, Workalemahu T, et al (2012). Meta-Analysis of 211,221 Individuals Identifies Novel Waist-Hip Ratio Loci Including Those Involved in Adipogenesis and Type 2 Diabetes. Author URL.

Wheeler E, Soranzo N, Sanna S, Gieger C, Radke D, Dupuis J, Stolerman E, Bouatia-Naji N, Langenberg C, Prokopenko I, et al (2009). A Large Genome-wide Association Study of Glycated Hemoglobin Identifies Ten Common Variants not Mediated Through BMI. Author URL.

Perry J, Zeggini E, Scott L, Saxena R, Voight B, Ferrucci L, Maggio M, Paolisso G, Sparso T, Langenberg C, et al (2009). Mendelian Randomization Studies of the Role of Biomarkers in Type 2 Diabetes. Author URL.

Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, McCullogh L, et al (2009). Novel Genetic Loci Implicated in Fasting Glucose Homeostasis and Their Impact on Related Metabolic Traits. Author URL.

Prokopenko I, Hottenga JJ, Aulchenko YS, Thorleifsson G, Dupuis J, Florez JC, Go MJ, Jackson AU, Kim YJ, Langenberg C, et al (2009). Variants in the DGKB Gene Influence Fasting Glucose Levels in Populations of European and East Asian Descent. Author URL.

Lindgren CM, Loos RJ, Li S, McCarthy MI, Wareham NJ, Barroso I, Consortium CO (2008). Association studies involving over 90,000 samples demonstrate that common variants near to MC4R influence fat mass, weight and risk of obesity. Author URL.

Sandhu MS, Weedon MN, Fawcett KA, Wasson J, Debenham SL, Daly A, Lango H, Frayling TM, Neumann R, Blech I, et al (2007). WFS1 is a type 2 diabetes susceptibility gene. Author URL.

Roccasecca RM, Bottomley BE, Fawcett K, O'Rahilly S, Wareham NJ, Barroso I (2006). Genotyping and biochemical characterization of a PPP1R3D frame-shift mutation identified in two insulin resistant subjects. Author URL.

Fawcett KA, Wareham NJ, O'Rahilly S, Sandhu MS, Barroso I (2006). The PSARL Leu262Val does not associate with fasting insulin levels in UK populations. Author URL.

Ines_Barroso Details from cache as at 2023-09-30 04:08:29

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External Engagement and Impact

Awards

Research.com ranked 10 in United Kingdom, and 120 in the world female Scientists.
Thomas Reuter Highly Cited Scientist and “World’s Most Influential Scientific Minds (2014-present)
Fellow of the Royal Society of Biology (FRSB) (2011-present)
Fellow of Darwin College (Cambridge) (2015-2019)
Ciência Viva Portugal Mulheres na Ciência (Tribute to Women in Science) (2016)
Scholarship of J.N.I.C.T (National Agency for Research) (1994-1996)
Commission of the European Communities, “Human Genome Analysis Programme”, Personal Research Bursary (1992-1993)

Committee/panel activities

Co-Chair,Wellcome Career Development Award Interview panel (2022 - present)
Diabetes UK Research Committee
Diabetes UK, IDia Faculty (Innovators in Diabetes)
SAB member, NHGRI-EBI GWAS Catalog (2015- present)
SAB member, Our future health (2021 - present)
SAB member, Novo Nordisk Foundation Center for Basic Metabolic Research (2020- present)
Sir Henry Dale Interview Committee panel member (Jan 2021- Dec 2021)
SAB member, Scottish Genomes Partnership (SGP) (2016 - 2019)
SAB member, Wellcome Trust Centre for Human Genetics, Oxford (2015- 2021)
Member of Jury for Novartis Health Science Accelerator - Programa SciCARE (Portugal)
Accelerating Detection of Disease genotyping chip design committee member
Member, Darwin College (Cambridge) Strategic Planning Committee (2016-2019)
External Diabetes Expert, Interview Panel member, Novo Nordisk Fellowship Programme, Oxford (May 2019)
Wellcome Trust Investigator Awards Expert Review Group; Genetics, Genomics and Population Research Panel Member (2011 – 2014)
Site Committee member of the evaluation of the Helmholtz (Berlin) Research-Programme "Cardiovascular and Metabolic Disease" (2013)

Editorial responsibilities

Faculty Opinions Computational Genomics & Genetic Analyses
Specialty Chief Editor, Frontiers in Genetic Disorders (2018 -2020)
Editorial Board, Global Health, Epidemiology and Genomics (2015 - 2020)
Editorial Board Member, Diabetologia (2013 – 2015)
Associate Editor, Diabetologia (2010 – 2012)

Invited lectures

(from 2016)

IGES symposium on Genomics for Global Precision Medicine part of ICHG, Feb 2023 in Cape Town
8th Meeting of the Study Group on the Genetics of Diabetes [SGGD], 11-13 May 2022 “The genetic architecture of human obesity, a continuum of causality”
EMGM, Plenary Speaker, April 2022, Cambridge “The genomic architecture of glycaemic traits across multiple ancestries"
ADA invited symposium presenter (25-29 Jun 2021 virtual) "From Discovery to Function in Obesity"
UCSD, invited seminar (13th May 2021, virtual) “The Trans-Ancestral Genomic Architecture of Glycaemic Traits”
GWAS summary statistics standards and sharing workshop, Chair of the Data content session (1-2 June 2020)
Genomic Medicine, 20-21 November 2019, Cambridge “The genetic lottery of obesity and thinness”
Novo Nordisk Fellowship Symposium Plenary Speaker, Oxford 2nd October 2019 “Genomic and Expression Signatures of Glycaemic Traits”
EASD, 16-19 September 2019, Barcelona “Unravelling the genetic aetiology of severe obesity”
Helmholtz Munich, 19th February 2019 “A journey of metabolic discovery: from rare disease and rare variant, to common trait and common variant”
University of Leeds 13th February 2019 “Genomic and Expression Signatures of Glycaemic Traits”
University of Exeter Medical School 28th November 2018 “Genetic studies of glycaemic traits provide insights into the biology of type 2 diabetes”
Wellcome Trust Advanced Course “Genetic Analysis of Mendelian and Complex Disorders”, 1-24 July 2018, Keynote Lecture
Quantitative Genomics 2018, 14th June 2018, UCL, London “Genomic and expression signatures of glycaemic traits”, Keynote speaker
Wellcome Centre Human Genetics, Oxford 11th June “A journey of metabolic discovery: from rare disease and rare variant, to common trait and common variant”
Towards a Functional Understanding of the Diabetic Genome, NIDDK meeting, April 23‐24 2018. “Genomic and Expression Signatures of Glycemic Traits”
Twelfth annual Angeline Heaton Lecture for the Human Medical Genetics and Genomics Program at the University of Colorado Anschutz Medical Campus, 22 Feb 2018 “Genes influencing type 2 diabetes, obesity and related traits”
Institute for Behavioral Genetics, Colloquium, CU Boulder Campus, 23 Feb 2018 “Genes influencing type 2 diabetes, obesity and related traits”
Plenary Lecture, Biomarkers and Assay Development Course, Faculty of Pharmacy, University of Lisbon, 6-10 Feb2017“Genomic Approaches to Metabolic Disease”
Keynote Speaker, Target Validation using Genomics and Informatics, EMBL Heidelberg, Germany 4 - 6 Dec 2016 “Impact of genetic variation on type 2 diabetes risk, diagnosis and complications in ancestrally diverse populations”
APCDR workshop “Big Data for Health in Africa” invited speaker “The Uganda Genome Project”, 3-4 Nov 2016
TGAC, Norwich Seminar, 26th Oct 2016, “Genes and Metabolism”
EMBO Workshop on Cell Size Regulation, 14 – 18 Sep 2016, Joachimsthal, Germany, Keynote “Genes influencing metabolism and size”
Plenary Lecture, Biomarkers and Assay Development Course, Faculty of Pharmacy, University of Lisbon, 6-10 Feb2017“Genomic Approaches to Metabolic Disease”
Keynote Speaker, Target Validation using Genomics and Informatics, EMBL Heidelberg, Germany 4 - 6 Dec 2016 “Impact of genetic variation on type 2 diabetes risk, diagnosis and complications in ancestrally diverse populations”
APCDR workshop “Big Data for Health in Africa” invited speaker “The Uganda Genome Project”, 3-4 Nov 2016
TGAC, Norwich Seminar, 26th Oct 2016, “Genes and Metabolism”
EMBO Workshop on Cell Size Regulation, 14 – 18 Sep 2016, Joachimsthal, Germany, Keynote “Genes influencing metabolism and size”

Teaching

Inês would be pleased to supervise research post-graduate students in her research specialism areas. If any of these are of interest please email her.

Supervision / Group

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Profile

Professor Inês Barroso

Professor of Diabetes

Overview

Qualifications

Links

Research

Research interests

Research projects

Publications

Journal articles

Abstract:GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Abstract:Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH

Abstract:Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Abstract:Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Abstract:An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript.

Abstract:Associations Between Glycemic Traits and Colorectal Cancer: a Mendelian Randomization Analysis.

Abstract:Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.

Abstract:Identification of Rare Loss-of-Function Genetic Variation Regulating Body Fat Distribution.

Abstract:Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations.

Abstract:The impact of population-level HbA1c screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis

Abstract:A polygenic resilience score moderates the genetic risk for schizophrenia

Abstract:Genome-wide association study identifies 48 common genetic variants associated with handedness.

Abstract:Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.

Abstract:Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Abstract:The importance of increasing population diversity in genetic studies of type 2 diabetes and related glycaemic traits.

Abstract:The trans-ancestral genomic architecture of glycemic traits.

Abstract:Complement genes contribute sex-biased vulnerability in diverse disorders

Abstract:Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

Abstract:Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.

Abstract:Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study.

Abstract:Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.

Abstract:Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Abstract:The influence of rare variants in circulating metabolic biomarkers.

Abstract:A linear mixed-model approach to study multivariate gene-environment interactions.

Abstract:Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract:Disentangling the genetics of lean mass.

Abstract:Genetic architecture of human thinness compared to severe obesity.

Abstract:Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance.

Abstract:Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Abstract:Mendelian Randomization Analysis of Hemoglobin A1c as a Risk Factor for Coronary Artery Disease.

Abstract:Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Abstract:Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:Author Correction: Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.

Abstract:Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.

Abstract:Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Abstract:DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

Abstract:Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Abstract:Genome-Wide Sequence Analysis of Kaposi Sarcoma-Associated Herpesvirus Shows Diversification Driven by Recombination.

Abstract:Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Abstract:Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls.

Abstract:Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Abstract:A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population is Associated with Fasting Insulin Levels and Type 2 Diabetes Risk.

Abstract:A two-stage inter-rater approach for enrichment testing of variants associated with multiple traits.

Abstract:An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.

Abstract:Correction: Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults.

Abstract:Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety.

Abstract:Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Abstract:Genetic aetiology of glycaemic traits: approaches and insights.

Abstract:Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

Abstract:Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults.

Abstract:Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

Abstract:Hypoinsulinaemic, hypoketotic hypoglycaemia due to mosaic genetic activation of PI3-kinase.

Abstract:Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis.

Abstract:Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Abstract:Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Abstract:Lyplal1 is dispensable for normal fat deposition in mice.

Abstract:Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Abstract:Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Abstract:Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Abstract:The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.

Abstract:Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.

Abstract:Whole-genome association study of antibody response to Epstein-Barr virus in an African population: a pilot.

Abstract:A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.

Abstract:Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: a Meta-analysis.

Abstract:Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings from the GLACIER and the MDC Studies.

Abstract:Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study.

Abstract:
GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Abstract:
Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH

Abstract:
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Abstract:
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Abstract:
An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript.

Abstract:
Associations Between Glycemic Traits and Colorectal Cancer: a Mendelian Randomization Analysis.

Abstract:
Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.

Abstract:
Identification of Rare Loss-of-Function Genetic Variation Regulating Body Fat Distribution.

Abstract:
Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations.

Abstract:
The impact of population-level HbA1c screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis

Abstract:
A polygenic resilience score moderates the genetic risk for schizophrenia

Abstract:
Genome-wide association study identifies 48 common genetic variants associated with handedness.

Abstract:
Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.

Abstract:
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Abstract:
The importance of increasing population diversity in genetic studies of type 2 diabetes and related glycaemic traits.

Abstract:
The trans-ancestral genomic architecture of glycemic traits.

Abstract:
Complement genes contribute sex-biased vulnerability in diverse disorders

Abstract:
Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

Abstract:
Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.

Abstract:
Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study.

Abstract:
Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.

Abstract:
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Abstract:
The influence of rare variants in circulating metabolic biomarkers.

Abstract:
A linear mixed-model approach to study multivariate gene-environment interactions.

Abstract:
Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract:
Disentangling the genetics of lean mass.

Abstract:
Genetic architecture of human thinness compared to severe obesity.

Abstract:
Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance.

Abstract:
Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Abstract:
Mendelian Randomization Analysis of Hemoglobin A1c as a Risk Factor for Coronary Artery Disease.

Abstract:
Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Abstract:
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:
Author Correction: Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.

Abstract:
Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.

Abstract:
Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Abstract:
DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

Abstract:
Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Abstract:
Genome-Wide Sequence Analysis of Kaposi Sarcoma-Associated Herpesvirus Shows Diversification Driven by Recombination.

Abstract:
Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Abstract:
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:
ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls.

Abstract:
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Abstract:
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Abstract:
A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population is Associated with Fasting Insulin Levels and Type 2 Diabetes Risk.

Abstract:
A two-stage inter-rater approach for enrichment testing of variants associated with multiple traits.

Abstract:
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.

Abstract:
Correction: Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults.

Abstract:
Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety.

Abstract:
Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Abstract:
Genetic aetiology of glycaemic traits: approaches and insights.

Abstract:
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

Abstract:
Genome-wide physical activity interactions in adiposity - a meta-analysis of 200,452 adults.

Abstract:
Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

Abstract:
Hypoinsulinaemic, hypoketotic hypoglycaemia due to mosaic genetic activation of PI3-kinase.

Abstract:
Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis.

Abstract:
Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Abstract:
Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Abstract:
Lyplal1 is dispensable for normal fat deposition in mice.

Abstract:
Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Abstract:
Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Abstract:
Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Abstract:
The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.

Abstract:
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.

Abstract:
Whole-genome association study of antibody response to Epstein-Barr virus in an African population: a pilot.

Abstract:
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.

Abstract:
Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: a Meta-analysis.

Abstract:
Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings from the GLACIER and the MDC Studies.

Abstract:
Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study.

Abstract:
Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: a Mendelian Randomisation Analysis.

Abstract:
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Abstract:
Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study.

Abstract:
Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.

Abstract:
Making sense of big data in health research: Towards an EU action plan.

Abstract:
Prospective functional classification of all possible missense variants in PPARG.

Abstract:
Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts.

Abstract:
The genetic architecture of type 2 diabetes.

Abstract:
The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

Abstract:
A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits.

Abstract:
Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy.