Overview

Luke is a research scientist in the Epidemiology and Public Health group at the University of Exeter. His research interests are broadly around understanding why some people are more susceptible than others for risk of age-related diseases. This includes pharmacogenetics, specific biological mechanisms (e.g., iron), and causes of multimorbidity.

Luke uses bioinformatic and statistical genetics techniques in large cohort data, especially the exceptional UK Biobank study that links genetics and medical records for up to 500,000 adults.

See the "Research" tab for details on current and past projects.

Qualifications

• 2015 PhD in Genomic Epidemiology (PCMD/UEMS)
• 2010 MSc Medical Informatics (Exeter)
• 2009 BSc Biological Sciences (Exeter)

Career

• 2022-            Senior Research Fellow in Genomic Epidemiology, UEMS
• 2015-2022     Post-doctoral researcher in Genomic Epidemiology, UEMS

Links

• Google Scholar profile
• GitHub
• A patient-focussed site to help people understand their risk of haemochromatosis once their genotype is known
• Twitter

Research group links

• Institute of Biomedical and Clinical Science

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Research

Research interests

Haemochromatosis

People with haemochromatosis absorb too much iron from their diet, which builds up in the body, damaging organs and causing disease. We investigated the most common haemochromatosis mutation and found that, despite the test being available, people are diagnosed too late. 1 in 156 people of northern European descent carry two copies of the mutation (called p.C282Y in gene HFE): we found that 1 in 5 of these males and 1 in 10 females aged 40 to 70 developed additional disease, compared to those without mutations (published in the BMJ in Jan 2019). In a second study we focussed on older people and found people with two copies of the mutation suffer from frailty and chronic pain, and had lower muscle strength (published in JGMS). These symptoms are often mistaken for "normal" ageing, and thus diagnosis is often missed. The condition is easily treated by removing blood, and blood tests for iron and genetic testing are simple and cost-effective. Therefore the research suggests that routine screening may be needed for people at risk of haemochromatosis.

Press release: https://www.exeter.ac.uk/news/featurednews/title_700061_en.html

We also made a patient-focussed site to help people understand their risk of haemochromatosis once their genotype is known: http://ex.ac.uk/ironoverload or https://sites.exeter.ac.uk/ironoverload

Multimorbidity: the GEMINI project

GEMINI: Genetic Evaluation of Multimorbidity towards INdividualisation of Interventions, https://sites.exeter.ac.uk/gemini/

The aim of our research is to uncover new links between long term conditions that could lead to improved interventions including drug treatments or other more focused treatments. These new links could include a better understanding of which cells in the body are most critical to the presence of two conditions in the same patient. The project uses genetic information to study the links between long term conditions, and Luke is integrating genetic and medical record information from UK Biobank (and published GWAS) with core team members Beth Voller, Ninon Mounier (https://medicine.exeter.ac.uk/people/profile/index.php?web_id=Ninon_Mounier), Tim Frayling (PI, https://medicine.exeter.ac.uk/people/profile/index.php?web_id=tim_frayling), and Jack Bowden (https://medicine.exeter.ac.uk/people/profile/index.php?web_id=Jack_Bowden).

Pharmacogenetics in cardiovascular prevention

Inherited genetic variants can modify the effectiveness of medications, contribution to inter-individual variability and susceptibility to side-effects. Luke has led several studies into key medications commonly prescribed to prevent cardiovascular disease, for example Clopidogrel is prescribed to reduce risk of embolism, yet over 25% of the UK population carry a genetic variant in gene CYP2C19 that reduces effectives and increases stroke risk by 50% (see our paper https://doi.org/10.1136/bmjopen-2021-053905)

Luke co-supervises PhD student Deniz Türkmen (https://medicine.exeter.ac.uk/people/profile/index.php?web_id=Deniz_Turkmen) who has led key studies into:

• Statins, prescribed to lower cholesterol, where we found that genetic variant SLCO1B1*5 reduced likelihood of meeting cholesterol targets, especially in women (https://doi.org/10.1111/bcp.15245)
• Calcium channel blockers, prescribed to reduce blood pressure. We found that incidence of side-effects such as Heart Failure were impacted by common variants; we estimated that HF incidence in CCB patients could be reduced by 9% if carriers of an RYR3 genetic variant could experience the same treatment effect as non-carriers (https://doi.org/10.1111/bcp.15541)

A methodological advancement in pharmacogenetic studies was made by collaborating with statistician Prof Jack Bowden on the TWIST (Triangulation within a Study) framework, published in PLoS Genetics (https://doi.org/10.1371/journal.pgen.1009783). Luke published the method as an open-source R package on GitHub for others to use (https://github.com/lukepilling/twistR).

Longevity, frailty, and sarcopenia

The release of genotype data in nearly 500,000 UK Biobank participants has transformed the field of genetic epidemiology. In combination with the extensive phenotyping and medical records linkage of the participants, the genetics provides unprecendented opportunities to understand mechanisms of disease and ageing, and causal evidence for biomarkers. We are utilizing this resource to identify specific sections of the genome that affect health and ultimately lifespan.

Mechanisms of disease: utilizing gene expression data

Using data from the InCHIANTI population study of ageing I have been looking into differential gene expression patterns in peripheral blood leukocytes that are associated with ageing and its pathologies. Using individual phenotype information such as cognitive performance, frailty, various metabolic and anatomic traits, and genome-wide expression data we can statistically assess differences in gene expression profiles between individuals with different characteristics, adjusted for potential confounding factors. In doing so we hope to reveal underlying cellular mechanisms linked to age-related diseases and phenotypes.

International collaborations with other large human cohorts, including the Framingham Heart Study and Rotterdam Study (as well as the CHARGE consortium), are becoming a major part of these analyses, increasing the robustness of our findings and strengthening ties with fellow researches in this fast-moving field.

Research networks

CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology)

BSRA (British Society for Research on Ageing)

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Publications

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Teaching

PhD supervision

Postgraduate Research opportunities: Dr Pilling is open to enquiries from students with their own funding interested in pursuing an MSc by Research or PhD in ageing, epidemiology, genetics, and related research.

Current

Bethany Voller (2022-2025, 1st supervisor) is undertaking genetic analyses in the context of multimorbidity, to understand shared causes and mechanisms.

Mitchell Lucas (2022-2025, 3rd supervisor) is undertaking analyses of haemochromatosis to undertstand penetrance: why some patients experience severe disease where others do not.

Completed

Deniz Türkmen (2020-2023, 2nd supervisor) performed pharmacogenetic analyses to characterise the effect of genetic variants on clinical outcomes during periods of drug prescribing. She has led studies on:

• Statins, prescribed to lower cholesterol, where we found that genetic variant SLCO1B1*5 reduced likelihood of meeting cholesterol targets, especially in women (https://doi.org/10.1111/bcp.15245)
• Calcium channel blockers, prescribed to reduce blood pressure. We found that incidence of side-effects such as Heart Failure were impacted by common variants; we estimated that HF incidence in CCB patients could be reduced by 9% if carriers of an RYR3 genetic variant could experience the same treatment effect as non-carriers (https://doi.org/10.1111/bcp.15541)

Dr Garan Jones (2018-2021, 2nd supervisor) undertook analysis of UK Biobank data to better understand genetic risk factors for physical frailty. He led a large 22-cohort genome-wide meta-analysis of sarcopenia (weakness) in older people, published in Nature Communications (https://doi.org/10.1038/s41467-021-20918-w). He is now postdoctoral Reseach Fellow at the University of Exeter with Prof Chrissie Thirlwell researching cancer genomics (https://medicine.exeter.ac.uk/people/profile/index.php?web_id=Garan_Jones).

Project student supervision

Luke supervises students from the MSc Genomic Medicine programme and BSc Medical Science programme undertaking research projects with the group.

He also assists with the Research SSU teaching of UEMS medical students - the students spend 3 weeks with our group learning the principals of research in epidemiology, and applying research techniques to real data to test hypotheses. This gives the prospective medical graduates an idea of how research is conducted, and how this might eventually be translated into medical practice.

Other Teaching

Luke assists with the facilitation of small-study group sessions for the BSc Medical Science programme 2nd-year Medical Genetics module.

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