Professor Adam Butterworth

Adam Butterworth

Professor of Molecular Epidemiology, BHF Cardiovascular Epidemiology Unit; Strategic Lead for Research and Enterprise, Department of Public Health and Primary Care

Email: asb38@medschl.cam.ac.uk

Twitter: @aidanbutty

LinkedIn: https://www.linkedin.com/in/adam-butterworth-1b0ba116b/

Mastodon/other social media:

Biography

 Following training in genetics at the University of Cambridge and genetic epidemiology at the University of Sheffield, Adam completed a PhD in meta-analysis of genetic association studies of coronary heart disease at the University of Cambridge. Since his PhD, Adam has worked in the Cardiovascular Epidemiology Unit, initially as a post-doctoral Research Associate, from 2012 as a University Lecturer in Cardiovascular Epidemiology, from 2018 as a Reader in Molecular Epidemiology, and since 2021 as Professor of Molecular Epidemiology, leading a research group of pre-doctoral and post-doctoral scientists in genomic and molecular epidemiology.

Outside of work, you will most likely find Adam playing, watching or coaching football, playing board games with his family, or feeding his addiction to flat whites!

Research Approach:

The group primarily focuses on large-scale genetic and molecular epidemiology analyses to understand causes of disease, with a primary focus on cardiometabolic diseases and molecular traits.

Genetic discovery: a core interest of the group revolves around the identification of genetic variation linked with cardiovascular diseases and related phenotypes (eg, vascular risk factors such as lipids).  For example, we recently led a million-person study that identified >200 genes related to risk of coronary heart disease. The group has also conducted pioneering studies to understand the genetic determinants of molecular ‘omics, such as plasma proteomics and metabolomics). Increasingly we are also trying to address the ‘genomic diversity’ problem by building and analysing studies of diverse ancestries around the world, including the BELIEVE and BRAVE studies in Bangladesh and the MAVERIK study in Malaysia.

Human genetics to inform therapeutics: By relating informative genetic variants (eg, variants associated with molecular ‘omics) to disease outcomes and phenotypes, inference about the likely efficacy and safety profile of therapeutic agents (or potential therapeutic agents) can be made. For example, in a recent study we used variants associated with plasma proteins and multi-tissue gene expression levels to identify pathways influencing risk of severe COVID-19 outcomes. The group has worked closely with several large pharmaceutical companies (e.g. Regeneron, AstraZeneca, Merck, Novartis, Biogen, Sanofi) to help discover and evaluate pathways of potential therapeutic interest for a wide range of disease areas, including cardiovascular, neurological and haematological disorders.

National and international consortia: Genetic and molecular epidemiology are inherently collaborative disciplines in which the most robust findings are produced by pooling data from across studies. We are closely involved in several major national and international initiatives to which we contribute data and play a leadership role, including:

• The HDRUK Multiomics Cohorts Consortium: Adam is the PI of this national consortium, which brings together 15 population cohorts from across the UK. The cohorts all have genomic data, linkage to electronic health records and some multi-omics data (e.g. transcriptomics, proteomics, metabolomics, lipidomics, epigenetics), allowing integrative molecular epidemiology studies of association, prediction and aetiology across common complex diseases;

• EPIC-CVD: Adam is the Scientific Coordinator of the EPIC-Heart/EPIC-CVD study, a pan-European study of incident coronary disease and stroke including participants from 23 centres across 10 European countries. This project has a wealth of genetic, biochemical and risk factor data, which are predominantly utilised for the study of gene-environment interaction, cardiovascular risk prediction, and genetic discovery;

• The International Hundred K+ Cohorts Consortium: the IHCC is a global consortium of large-scale population cohorts designed to address questions that single cohorts cannot reliably answer. As of 2022, the consortium involves >70 cohorts and a total of >52 million participants. Adam sits on the Scientific Strategy and Enhancements Committee of the IHCC.

Current projects: Key current initiatives include multi-ethnic discovery analyses of cardiometabolic diseases and molecular traits, interrogation of novel domains of multi-omics (eg, phoshoproteomics, glycomics, mass spec proteomics), and therapeutic target discovery for common and rare diseases (eg, sickle cell disease).

Selected Publication 

1. Surendran et al, Rare and common genetic determinants of metabolic individuality and their effects on human health. Nature Medicine 2022; 28(11):2321-2332.
2. Aragam et al, Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants. Nature Genetics 2022; 54(12):1803-1815.
3. Gaziano et al, Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19. Nature Medicine 2021; 27(4):668-676.
4. Zheng et al, Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nature Genetics 2020; 52(10):1122-1131.
5. Sun et al, Genomic atlas of the human plasma proteome. Nature 2018; 558(7708):73-79.

Research collaborators

Professor Claudia Langenberg, Queen Mary University of London / Berlin Institute of Health

Professor James Peters, Imperial College London

Professor Johannes Kettunen, University of Oulu

Dr Krishna Aragam, Mass General Research Institute

Professor Nicole Soranzo, Human Technopole / Wellcome Sanger Institute