Nat Commun. 2026 Feb 27. doi: 10.1038/s41467-026-69982-0. Online ahead of print.
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 < 5×10-8); 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 < 2.5×10-6). 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.
PMID:41760662 | DOI:10.1038/s41467-026-69982-0