A Mendelian randomization study revealed that genetically predicted endogenous testosterone is positively linked to cardiovascular disease (CVD), including thromboembolism, heart failure (HF), and myocardial infarction (MI) in men. The study identified genetic predictors of endogenous testosterone from a genome wide association study of serum testosterone conducted in 3225 men of European ancestry aged 50-75. The predictors were assessed in 392 038 white British men and women aged 40-69. In men, endogenous testosterone genetically predicted by variants in the JMJD1C gene region was positively associated with thromboembolism (odds ratio per unit increase in log transformed testosterone (nmol/L) 2.09) and HF (7.81), but not MI (1.17). Associations were less obvious in women. The findings were validated in 171 875 patients of about 77% European descent, in that genetically predicted testosterone (based on JMJD1C gene region variants) was positively associated with MI (1.37). However, testosterone genetically predicted by potentially pleiotropic variants in SHBG gene region had no association with the outcomes. The findings are consistent with other studies and provide another strand of evidence in sex hormone related mechanisms in CVD. Source: https://www.bmj.com/
