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

    CM Schooling, Shan Luo, Shiu Lun Au Yeung, Deborah J. Thompson, Savita Karthikeyan, Thomas Bolton, Amy M. Mason, Erik Ingelsson, Stephen Burgess
    TLDR Testosterone is linked to cardiovascular risk factors and stroke, but its exact role is unclear.
    The study used Mendelian randomization to investigate genetic predictors of testosterone and their associations with cardiovascular disease (CVD) and related risk factors. It analyzed genetic variants in the SHBG and JMJD1C gene regions in large cohorts, including 171,191 individuals from the CARDIoGRAMplusC4D consortium and 367,643 individuals from the UK Biobank. The findings indicated that higher genetically predicted testosterone levels were associated with increased CVD risk in men but not in women. The study highlighted sex-specific differences and suggested that testosterone-lowering therapies might benefit men at high risk of CVD. However, it also noted inconsistencies between gene regions and the need for further research to understand the biological mechanisms and the potential impact of testosterone interventions on cardiovascular health.
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