EP News: Basic and Translational

  • Nipavan Chiamvimonvat
    Address reprint requests and correspondence: Dr Nipavan Chiamvimonvat, Department of Internal Medicine and Pharmacology, University of California, Davis, GBSF 6315, 451 Health Science Dr, Davis, CA 95616.
    Department of Internal Medicine and Pharmacology, University of California, Davis, Davis, California
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Published:November 17, 2022DOI:
      Levin et al (Nat Commun 2022;13:6914, PMID 36376295) performed a multi-ancestry genome-wide association study meta-analysis of all-cause heart failure including 115,150 cases and 1,550,331 controls and identified 47 risk loci. Multivariate genome-wide association studies were performed that integrate heart failure with related cardiac magnetic resonance imaging endophenotypes, identifying 61 risk loci. Colocalization, gene expression profiling, and Mendelian randomization provide convergent evidence for the roles of BCKDHA (a gene encoding for branched chain keto acid dehydrogenase E1 subunit alpha) and circulating branched-chain amino acids in heart failure and cardiac structure. Finally, proteome-wide Mendelian randomization identifies 9 circulating proteins associated with heart failure or quantitative imaging traits. The authors conclude that the study highlight similarities and differences among heart failure, implicating common genetic variation in the pathogenesis of heart failure, and identify circulating proteins that may represent cardiomyopathy treatment targets.
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