Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study

Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes. Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method. Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62-0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67-0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59-0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47-0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (β 0.07, 95% CI 0.04-0.10, P < 0.001), lower levels of testosterone in women (β -0.13, 95% CI-0.16 to-0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64-0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52-1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed. Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.