The causal effect of metabolic syndrome and its components on benign prostatic hyperplasia: A univariable and multivariable Mendelian randomization study

Abstract

BackgroundPrevious observational studies have indicated that metabolic abnormalities are associated with benign prostatic hyperplasia (BPH). The limitations of the research methodology of observational studies do not allow causal inference to be drawn; however, Mendelian randomization (MR) can clarify this.MethodsUsing summary‐level data from genome‐wide association studies, we conducted a two‐sample MR study to examine the causality of the metabolic syndrome (MetS) and its components on BPH (26,358 BPH cases and 110,070 controls). The random‐effects inverse‐variance weighted was employed as the primary method for MR analyses.ResultsWe observed that genetically predicted waist circumference (WC) (odds ratio [OR] = 1.236, 95% confidence interval [CI]: 1.034−1.478, p = 0.020) and diastolic blood pressure (DBP) (OR = 1.011, 95% CI: 1.002−1.020, p = 0.020) were significantly positively associated with BPH risk. We did not identify a causal effect of MetS (OR = 0.975, 95% CI: 0.922−1.031, p = 0.375), systolic blood pressure (OR = 1.004, 95% CI: 0.999−1.008, p = 0.115), triglycerides (OR = 1.016, 95% CI: 0.932−1.109, p = 0.712), high‐density lipoprotein (OR = 1.005, 95% CI: 0.930−1.086, p = 0.907), and fasting blood glucose (OR = 1.037, 95% CI: 0.874−1.322, p = 0.678) on BPH. In the multivariable MR analysis, we observed that the risk effect of DBP (OR = 1.013, 95% CI: 1.000−1.026, p = 0.047) on BPH persisted after conditioning with WC (OR = 1.132, 95% CI: 0.946−1.356, p = 0.177).ConclusionsOur study provides genetic evidence supporting the causal effect of DBP on BPH, although the effect of WC needs to be further validated.

The impact of obesity and sexual behavior on prostate cancer risk is mediated by testosterone levels: a mendelian randomization study and mediation analysis

“…MR has been previously utilized to investigate potential risk factors for PCa that have been reported in several observational studies, including coffee intake, 41 , 42 smoking, 43 , 44 alcohol consumption, 43 , 45 and vitamin E. 46 , 47 However, the MR results for these factors have always been negative. 48 , 49 , 50 , 51 After reviewing these MR studies, we discovered that some did not stratify the exposed population by sex or ancestry. This can result in population heterogeneity, which may cause instability in the results, particularly for two-sample MR, a frequently used method in current MR research.…”