Genome-wide analysis of cardiac ventricular phenotypes reveals novel loci and therapeutic targets for heart failure.
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Authors
Nicholls H.L.
Vargas J.D.
Sanghvi M.M.
Ahn H.S.
Chahal C.A.A.
Khanji M.Y.
Petersen S.E.
Munroe P.B.
Aung, N.
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2026
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Abstract
Left and right ventricular imaging measures are essential for heart failure diagnosis and prognostication, yet their genetic architecture remains underexplored. We conduct genome-wide association analyses of twenty left and right cardiovascular magnetic resonance phenotypes in 56, 509 UK Biobank participants, including conventional measurements (e.g., volumes/ejection fraction) and novel parameters (left ventricular global function index and myocardial contraction fraction). We identify 200 loci associated with at least one phenotype (P < 5x10-8); 58 being novel. A polygenic risk score for left ventricular global function index negative associates with heart failure in phenome-wide scan. Rare variant analysis reveals enrichment of deleterious variants across 13 genes (P < 2.5x10-6). Colocalisation with heart failure implicates 23 shared loci and bioinformatic analysis prioritises genes including HSPB7, CAMK2D, ALDH2, ENG, and YWHAE. Druggability analysis highlights PDE3A, informing divergent effects of non-selective PDE3 inhibition. In this work, we expand our knowledge of cardiac ventricular genetics, suggesting potential heart failure therapeutic targets. Copyright © 2026. The Author(s).
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Nature communications