The genetic aetiology of hypertropic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular condition that affects 1 in 500 individuals and is a leading cause of sudden cardiac death. Whilst traditionally considered to be a monogenic, autosomal dominant condition, current clinical genetic testing strategies fail to explain most (~60%) cases of HCM. Following the recruitment of many individuals with (n= >10,000) and without the disease (n= >100,000), my research uses a combination of statistical and computational approaches to better understand the genetic basis of HCM and contributes to an MRC strategic skill priority (Living a long & healthy life: Molecular datasets and disease). This advances my previous training within clinical medicine, computational biology and statistics, by providing training in cutting-edge clinical statistics and bioinformatic techniques (Professor Farrall) and clinical research and molecular biology (Professor Watkins). Consequently, this fulfills a cross-cutting interdisciplinary skills theme outlined by the MRC.
As part of an international network of collaborators, I will look to provide robust statistical evidence to either support or refute proposed inheritance models underpinning HCM, using available next-generation sequencing data. In addition, my work will focus on the impact variants associated with HCM have upon heart muscle function within the 'normal' population. This will refine our understanding of myocardial biology and contribute towards the elucidation of underlying disease mechanisms, which we hope will improve our understanding of the pathophysiology of HCM and facilitate improved patient care.