Andrew Harper (2017-2020)
Project: The genetic architecture of hypertrophic cardiomyopathy
Supervisor: Prof Hugh Watkins, Prof Martin Farrall and Dr. Anuj Goel
Having completed a Masters in Medical Genetics during medical school, my clinical approach as a physician has always been focussed on trying to better understand the root cause of disease. Experience working as part of a clinical team delivering care to patients, and their families, with inherited cardiac conditions highlighted to me how critical this philosophy was. Knowing which specific genetic variant was causal of disease was a cornerstone in the delivery of care, as it provided actionable information that facilitated screening and risk stratification. But unfortunately, all too often, a variant was not identifiable. This was particularly true for hypertrophic cardiomyopathy, a relatively common genetic condition that affects ~1/500 individuals and remains a leading cause of sudden death, embolic stroke and heart failure in early and mid-adult life.
These clinical experiences motivated me to further explore the genetic basis of inherited cardiac conditions. Having previously performed genetic association studies for common, genetically complex heart conditions as part of my Masters, I was able to integrate clinical training with academic pursuit in Professor Hugh Watkin’s lab. This began with funding from the NIHR, as part of the Academic Foundation Programme in Oxford, that enabled me to study the functional consequences of candidate genes in cardiomyopathy. Throughout Core Medical Training in London I established collaborations with leaders in the field of cardiomyopathy and refined my hypotheses. The opportunity to formally pursue a DPhil was provided through a Radcliffe Department of Medicine scholarship funded by the MRC. This has allowed me to comprehensively evaluate the contribution rare and common genetic variants make towards hypertrophic cardiomyopathy and has revealed clinically important findings. This includes the realisation that: 1) a variant, often cited as being causal of disease is in fact benign. An important finding considering over 100 million people worldwide harbour the variant; and 2) common variation throughout the genome can increase an individual’s susceptibility to developing hypertrophic cardiomyopathy.
Since completing my studies, I have re-commenced clinical training and continue to evaluate the contributions genetics makes towards human disease as a Genomic Sciences Physician and Medical Director (Early Respiratory & Immunology Clinical Development) at AstraZeneca. I hope to use the knowledge and skills acquired throughout my DPhil to deliver transformational therapies to patients with large unmet medical needs.