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Nat Commun DOI:10.1038/s41467-020-15823-7

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

Publication TypeJournal Article
Year of Publication2020
AuthorsPirruccello, JP, Bick, A, Wang, M, Chaffin, M, Friedman, S, Yao, J, Guo, X, Venkatesh, BAmbale, Taylor, KD, Post, WS, Rich, S, Lima, JAC, Rotter, JI, Philippakis, A, Lubitz, SA, Ellinor, PT, Khera, AV, Kathiresan, S, Aragam, KG
JournalNat Commun
Volume11
Issue1
Pages2254
Date Published2020 May 07
ISSN2041-1723
Abstract

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.

DOI10.1038/s41467-020-15823-7
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/32382064?dopt=Abstract

Alternate JournalNat Commun
PubMed ID32382064
Grant List1R01HL139731 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
R01HL128914 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
K24HL105780 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
HL127564 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
18SFRN34250007 / / American Heart Association (American Heart Association, Inc.) /
18SFRN34110082 / / American Heart Association (American Heart Association, Inc.) /
17IFUNP33840012 / / American Heart Association (American Heart Association, Inc.) /
14CVD01 / / Fondation Leducq /