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Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. We assessed genetic associations of variants in two gene regions that are predictors of testosterone (SHBG and JMJD1C) with several cardiovascular risk factors, coronary artery disease risk and ischaemic stroke risk. There was some evidence of an association for variants in these regions with risk of CAD and with ischaemic stroke in men. This implies that sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear.
Evaluation of the causal relation between hematocrit, hemoglobin, HbA1c, testosterone and cardiovascular outcomes in the UK Biobank using Mendelian randomization analysis
The aims of this study are to examine the causal effect of testosterone, HbA1c, hemoglobin and hematocrit on CVD risk factors, prevalent CVD and CVD deaths using Mendelian randomization analysis, with the relevant genetic variants as instruments in the UK Biobank. The proposed research will help investigate how these potential targets of intervention influence population health using Mendelian randomization design which is less susceptible to confounding than observational studies. The results will provide additional insights concerning the drivers of cardiovascular disease, with corresponding implications for public health policies and the development of interventions. We compare cardiovascular events and risk factors according to levels of genetically determined hematocrit, hemoglobin, HbA1c and testosterone. 500,000 participants (full cohort) for the analysis involving hematocrit, hemoglobin, HbA1c and genetic data. We will restrict the analysis involving testosterone and relevant genetic data among men.