The Walsh CardioGenomics Lab investigates the complex genetics of heritable cardiac diseases that can cause heart failure and sudden death in the young. We aim to discover and characterise the genetic factors associated with these conditions and translate these findings to enhance diagnosis, risk prediction and clinical management in patients, families and the population at large.
Our research focuses on exploring the novel complex aspects of the genetic architecture of cardiomyopathies and arrhythmia syndromes - beyond the established Mendelian genetics that is the basis of current clinical application. This includes defining the spectrum of associations for cardiac genes (across phenotype, zygosity, variant class and frequency/effect size), exploring novel variant classes of intermediate effect size in the coding and non-coding genome, pursuing research in diverse populations and patient groups, and developing integrated and comprehensive genetic risk profiling. See our research page for more details.
Cardiomyopathies
Cardiomyopathies are structural heart diseases that affect ~1/200 people and can lead to heart failure and sudden cardiac death in the young and middle-aged. Their genetic aetiology is complex - rare Mendelian-like variants are detected in about one-third of patients but these variants are characterised by incomplete penetrance and variable expressivity. Other genetic risk factors, including a strong polygenic component, are now being explored and evaluated for clinical application.
Inherited arrhythmia syndromes cause defects in the electrical system of the heart and can lead to abrnomal rhythms and sudden cardiac death in structurally normal hearts of young people. LQTS and CPVT both have a strong Mendelian genetic architecture, with a high yield of rare causal variants. In contrast, Brugada syndome has a highly complex aetiology and a unique geographical epidemiology, being several times more prevalent in East/Southeast Asia than other regions.
Cardiovascular Research Insititute
City St. George's University of London