Gene-based map of cardiovascular diseases

Missense- and pathogenic-variant burden testing in up to 483,311 UK Biobank participants identified 86 exome-wide significant cardiovascular gene–phenotype associations, including 46 novel links.

• Why it matters: Rare coding variants likely contribute to cardiovascular disease, but how functionally informed variant classification and sex-specific effects shape gene–phenotype associations across disease groups is not well characterized.
• What they did: Whole-genome sequencing from up to 483,311 UK Biobank participants across six ancestry groups and eight cardiovascular phenotypes was analyzed with state-of-the-art missense classification and predicted pathogenic germline variants, using combined-sex and sex-stratified tests plus cross-ancestry meta-analysis.
• The result: After cardiometabolic adjustment, 60 associations remained exome-wide significant and 18 additional associations emerged, and penetrance estimates among qualifying-variant carriers showed variant selection affects interpretation of inherited susceptibility.

AI summary of the abstract · may contain errors · not medical advice · read the paper.