Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy

• Published in: Nature communications Vol. 11; no. 1; p. 2254
• Main Authors: Pirruccello, James P, Bick, Alexander, Wang, Minxian, Chaffin, Mark, Friedman, Samuel, Yao, Jie, Guo, Xiuqing, Venkatesh, Bharath Ambale, Taylor, Kent D, Post, Wendy S, Rich, Stephen, Lima, Joao A C, Rotter, Jerome I, Philippakis, Anthony, Lubitz, Steven A, Ellinor, Patrick T, Khera, Amit V, Kathiresan, Sekar, Aragam, Krishna G
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 07.05.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Arteriosclerosis; Atherosclerosis; Cardiomyopathy; Cardiomyopathy, Dilated - diagnostic imaging; Cardiomyopathy, Dilated - genetics; Congestive heart failure; Dilated cardiomyopathy; Genetic diversity; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Heart; Heart - diagnostic imaging; Heart transplantation; Humans; Loci; Magnetic Resonance Imaging; Medical imaging; Mutation; Myocardium - metabolism; Pathogenesis; Polymorphism, Single Nucleotide - genetics; Resonance; Structure-function relationships; Transplantation; Ventricle
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15823-7

Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.