| Title: | Genome-wide analysis of cardiac ventricular phenotypes reveals novel loci and therapeutic targets for heart failure |
| Journal: | Nature Communications |
| Published: | 27 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41760662/ |
| DOI: | https://doi.org/10.1038/s41467-026-69982-0 |
| URL: | http://dx.doi.org/10.1038/s41467-026-69982-0 |
Publication 17603
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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 < 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.</p>
9 Authors
- Hannah L. Nicholls
- Jose D. Vargas
- Mihir M. Sanghvi
- Hyo-Suk Ahn
- C. Anwar A. Chahal
- Mohammed Y. Khanji
- Steffen E. Petersen
- Patricia B. Munroe
- Nay Aung
1 Application
| Application ID | Title |
|---|---|
| 2964 | Description of cardiovascular phenotype in the UK Biobank population based on cardiovascular magnetic resonance and carotid ultrasound |
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