Evaluating the relationship between educational attainment, obesity-related indicators, and prostate diseases: A univariable and multivariable Mendelian randomization study

Recent studies have highlighted the effects of educational attainment (EA) and obesity on health, but their exact causal associations with prostate diseases remain unclear. Therefore, in this study, we performed a Mendelian randomization study to explore these potential relationships. Instrumental variables (IVs) for EA, obesity-related indicators (waist-to-hip ratio [WHR], body mass index, and leptin, and adiponectin [APN] levels), and 3 prostate diseases (benign prostatic hyperplasia [BPH], prostate cancer [PCa], and prostatitis) were selected from genome-wide association studies. Univariate and multivariate Mendelian randomization analyses were performed to investigate and verify the causal relationships. Univariate Mendelian randomization revealed that higher EA levels were related with a lower risk of prostatitis (odds ratio [OR] = 0.819; 95% confidence interval (CI): 0.742-0.905) and a higher risk of PCa (OR = 1.112; 95% CI: 1.060-1.167) and BPH (OR = 1.071; 95% CI: 1.019-1.126). WHR was positively correlated with BPH (OR = 1.13; 95% CI: 1.035-1.352), and leptin was negatively related with PCa (OR = 0.834; 95% CI: 0.912-1.160). Sensitivity analysis revealed little evidence of bias. Multivariate Mendelian randomization further clarified that EA exerted directly on prostatitis after adjusting for alcohol consumption (OR = 0.799; 95% CI: 0.691-0.923) and smoking (OR = 0.784; 95% CI: 0.662-0.927). After accounting for drinking, WHR was found to have a detrimental effect on prostatitis (OR = 1.184; 95% CI: 1.032-1.359) and BPH (OR = 1.177; 95% CI: 1.035-1.338). Leptin demonstrated a protective role against PCa (OR = 0.788, 95% CI: 0.619-1.004, adjusted for alcohol consumption), while APN was not associated with PCa, which may differ from previous studies. Our study highlights the role of EA and obesity in the progression of prostate disease, provides novel insights into the mechanisms of the relationship between central obesity, leptin, APN, and prostate disease, and indicated that leptin receptor antagonists are promising treatments for PCa.