Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-15823-7
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Funding
- TOPMed Informatics Research Center [3R01HL-117626-02S1, HHSN268201800002I]
- TOPMed Data Coordinating Center [3R01HL-120393-02S1, HHSN268201800001I]
- National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, DK063491]
- NHLBI
- National Institutes of Health [RO1 HL127564]
- National Human Genome Research Institute of the US National Institutes of Health [5UM1HG008895]
- Ofer and Shelly Nemirovsky Research Scholar Award from Massachusetts General Hospital
- American Heart Association Institute for Precision Cardiovascular Medicine [17IFUNP33840012]
- John S. LaDue Memorial Fellowship for Cardiovascular Research
- NIH [1R01HL139731, 1RO1HL092577, R01HL128914, K24HL105780]
- American Heart Association [18SFRN34250007, 18SFRN34110082]
- Fondation Leducq [14CVD01]
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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. Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known. Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM.
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