Abstract
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.
Highlights
It is well-established that educational attainment (EA) is an essential social determinant of health [1]
For the four oncological diseases, the primary analysis using Inverse variance weighted (IVW) suggested that genetically predicted one standard deviation (SD) increase in EA was causally correlated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05–1.25, P = 0.003], while no causal effect was observed for bladder cancer, kidney cancer, and testicular cancer (Figure 2)
In terms of the five non-oncological diseases, the results from IVW showed that genetically predicted one SD increase in EA was correlated with a decreased risk of kidney stone and cystitis after Bonferroni correction and suggestively correlated with a lower risk of prostatitis and incontinence (Figure 2)
Summary
It is well-established that educational attainment (EA) is an essential social determinant of health [1]. Existing observational studies are vulnerable to confounding factors and reverse causality. Mendelian randomization (MR) is a genetic epidemiological method that applies genetic variants, such as single nucleotide polymorphisms (SNPs), to estimate the causal effect of an exposure (e.g., EA) on an outcome (e.g., kidney stone). Compared with conventional observational studies, this method is less vulnerable to confounding factors and reverse causation and has been widely used in current epidemiological studies [19]. The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. We used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes
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