title: Genetics and genomics of dilated cardiomyopathy and systolic heart failure.
abstract: Heart failure is a major health burden, affecting 40 million people globally. One of the main causes of systolic heart failure is dilated cardiomyopathy (DCM), the leading global indication for heart transplantation. Our understanding of the genetic basis of both DCM and systolic heart failure has improved in recent years with the application of next-generation sequencing and genome-wide association studies (GWAS). This has enabled rapid sequencing at scale, leading to the discovery of many novel rare variants in DCM and of common variants in both systolic heart failure and DCM. Identifying rare and common genetic variants contributing to systolic heart failure has been challenging given its diverse and multiple etiologies. DCM, however, although rarer, is a reasonably specific and well-defined condition, leading to the identification of many rare genetic variants. Truncating variants in titin represent the single largest genetic cause of DCM. Here, we review the progress and challenges in the detection of rare and common variants in DCM and systolic heart failure, and the particular challenges in accurate and informed variant interpretation, and in understanding the effects of these variants. We also discuss how our increasing genetic knowledge is changing clinical management. Harnessing genetic data and translating it to improve risk stratification and the development of novel therapeutics represents a major challenge and unmet critical need for patients with heart failure and their families.
authors.affiliation: National Heart Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK.|Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK.
authors.forename: Upasana
authors.identifier: 0000-0003-2262-4626
authors.initials: U
authors.lastname: Tayal
authors.affiliation: National Heart Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK.|Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Prasad
authors.affiliation: National Heart Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK. stuart.cook@duke-nus.edu.sg.|Duke National University Hospital, 8 College Road, Singapore, 169857, Singapore. stuart.cook@duke-nus.edu.sg.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Cook
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D019468:Disease Management; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D023281:Genomics; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000235:genetics*; D006801:Humans