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A study was conducted to identify genes that influence calcific aortic stenosis (CAS), the most common valvular heart disease in older adults, through genome-wide association studies (GWAS). The study identified 23 lead variants in the GWAS, representing 17 unique genomic regions, of which 14 were significant in replication. Five replicated genomic regions were previously known risk loci for CAS, and six were novel. Two novel lead variants were associated with non-White individuals. Mendelian randomization and phenome-wide association study highlighted the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of CAS. In addition, the study clarified the shared and differential genetic architectures of CAS with atherosclerotic cardiovascular diseases.
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