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

TitleAnalysis 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
Pagination2254
Date Published2020 05 07
ISSN2041-1723
KeywordsCardiomyopathy, Dilated, Genome-Wide Association Study, Heart, Humans, Magnetic Resonance Imaging, Myocardium, Polymorphism, Single Nucleotide
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
Alternate JournalNat Commun
PubMed ID32382064
PubMed Central IDPMC7206184
Grant ListN01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL139731 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
UM1 HG008895 / HG / NHGRI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States