Key result
Shared common variants explain ~13% of phenotypic comorbidity across major cardiovascular disease pairs.
Why the study?
Cardiovascular diseases frequently co-occur, yet the shared genetic basis of cardiovascular multimorbidity remains unclear.
Observational (n=1,700,000)
Yes
This large-scale genomic study of ~1.7 million individuals defines a shared genetic framework for cardiovascular multimorbidity across eight major cardiovascular diseases, organizing them into three latent genetic clusters driven largely by systemic metabolic risk factors, body composition, and vascular biology.
Answers are grounded in this paper and cite their sources.
Genetic correlations may refine multimorbidity risk models; leaves open causal mechanisms and clinical utility pending prospective validation.
Cardiovascular diseases (CVDs) frequently co-occur, yet the shared genetic basis of cardiovascular multimorbidity remains unclear. We analysed common- and rare-variant genetic overlap across eight major CVDs using genome-wide and exome-wide association data from ∼1.7 million individuals in European and East Asian biobanks. Fifteen CVD pairs showed significant genetic correlations, with shared common-variant covariance explaining a modest proportion of phenotypic comorbidity. Genomic structural equation modelling identified three latent genetic clusters, while pleiotropic loci and genes frequently spanned cluster boundaries. Prioritised genes converged on atherosclerosis-related processes, myocardial structural and electrical programmes, and vascular-wall biology. In conditional analyses, body composition and metabolic traits consistently attenuated shared genetic liability, whereas circulating biomarkers showed smaller effects. For adequately powered traits, common-variant architecture was broadly similar between European and East Asian ancestries. These results define a shared genetic framework for cardiovascular multimorbidity centred on systemic risk factors and vascular biology.
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Romero et al. (2026) conducted an observational in Cardiovascular diseases (abdominal aortic aneurysm, aortic valve stenosis, atrial fibrillation, conduction disorders, heart failure, ischemic heart disease, venous thromboembolism, varicose veins) (n=1,700,000). Common and rare genetic variants across eight cardiovascular diseases vs. Unaffected controls / cross-trait genetic comparison was evaluated on Shared genetic architecture and bivariate genetic correlation (rg) across eight cardiovascular diseases. Common-variant genetic covariance was significant across 15 of 28 cardiovascular disease pairs (rg 0.10 to 0.66) and explained a median 12.8% of phenotypic comorbidity.
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