Genome-wide association and multi-omic analyses reveal new mechanisms for Heart Failure

Marios Arvanitis, Yanxiao Zhang, Wei Wang, Adam Auton, 23andMe Research Team, Ali Keramati, Neil Chi, Bing Ren, Wendy S. Post, Alexis Battle

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Sep 18, 2019
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Received Date: 2nd August 19

Heart failure is a major medical and economic burden in the healthcare system affecting over 23 million people worldwide. Although recent pedigree studies estimate heart failure heritability around 26%, genome-wide association studies (GWAS) have had limited success in explaining disease pathogenesis. We conducted the largest meta-analysis of heart failure GWAS to-date and replicated our findings in a comparable sized cohort to identify one known and two novel variants associated with heart failure. Leveraging heart failure sub-phenotyping and fine-mapping, we reveal a putative causal variant found in a cardiac muscle specific regulatory region that binds to the ACTN2 cardiac sarcolemmal gene and affects left ventricular adverse remodeling and clinical heart failure in response to different initial cardiac muscle insults. Via genetic correlation, we show evidence of broadly shared heritability between heart failure and multiple musculoskeletal traits. Our findings extend our understanding of biological mechanisms underlying heart failure.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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