Genetic Predictors of Testosterone and Their Associations with Cardiovascular Disease and Risk Factors: A Mendelian Randomization Investigation

The study investigated the causal role of testosterone in cardiovascular disease (CVD) using Mendelian randomization, focusing on genetic variants in the SHBG and JMJD1C gene regions. It included data from the CARDIoGRAMplusC4D consortium (171,191 individuals) and the UK Biobank (367,643 individuals). Genetic predictors of increased serum testosterone were linked to lipids, blood pressure, and height, with some evidence of association with coronary artery disease (CAD) and ischaemic stroke, particularly in men. However, the associations with some control outcomes were contrary to expectations. The study concluded that sex hormone-related mechanisms are relevant to cardiovascular risk factors and stroke, but the findings' applicability to endogenous testosterone or supplementation remains unclear, highlighting a limitation of Mendelian randomization due to uncertain biological functions of genetic variants.