A Mendelian randomization study on causal effects of leisure sedentary behavior on the risk of erectile dysfunction

Erectile dysfunction has been associated with leisure sedentary behavior in several epidemiological and observational studies. However, the interpretation of these findings is difficult due to residual confounding or reverse causality. To explore the causal association between leisure sedentary behavior and erectile dysfunction, and to explore the underlying mechanism using Mendelian randomization. In the present study, publicly available large-scale genome-wide association studies of leisure sedentary behaviors (television watching, computer use, and driving), erectile dysfunction, sex hormones (total testosterone, bioactive testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and sex hormone binding globulin), biomarkers of endothelial function (C reactive protein, E-selectin, and matrix metalloproteinase 7), and psychiatric symptoms (depression and anxiety) were used to perform two-sample Mendelian randomization analyses. The inverse variance weighting method was the main method used to estimate the association, and sensitivity analyses were also performed. A greater risk of erectile dysfunction was significantly associated with a higher genetic susceptibility to leisure computer usage (odds ratio = 3.57; 95% confidence interval = 1.78-7.16; p < 0.001). No evidence was obtained to suggest that watching television or driving for leisure increased the risk of erectile dysfunction. No association was found between computer use and depression, anxiety, C reactive protein, E-selectin, matrix metalloproteinase 7, or other sex hormones, with the exception of follicle-stimulating hormone levels (odds ratio = 0.29; 95% confidence interval = 0.12-0.69; p = 0.01). No indication of heterogeneity or pleiotropy was identified by sensitivity analysis. Extended computer usage for leisure raised the likelihood of developing erectile dysfunction, which may be associated to lower follicle-stimulating hormone levels; however, the role of endothelial dysfunction and psychological disorders in the development of erectile dysfunction should not be underestimated. Moderate physical activity may help to correct the dysfunction. The present study offered substantial evidence for a positive causal association between computer use and the risk of erectile dysfunction. However, a definitive causal association needs to be established by further research.