Genome-Wide European Ancestry Study Identifies Coronary Artery Disease-Associated Loci Through Gene-Sex Hormone Interaction

Although sex differences in coronary artery disease (CAD) risk have been observed, little is known about the role of sex hormones in CAD genetics. Accounting for sex hormone levels may help identify CAD-risk loci and extend our knowledge of its genetic architecture. A total of 365 662 individuals of European ancestry enrolled in the UK Biobank were considered. Genetic interaction of total testosterone, bioavailable testosterone, and SHBG (sex hormone-binding globulin) were evaluated. Gene-environment interactions in millions of samples software was used to conduct sex-stratified genome-wide interaction analysis with prevalent CAD as the outcome. Participant age at enrollment and principal components 1 to 10 were adjusted as covariates. We identified 45 loci in men and 8 loci in women that reached genome-wide significance (