前列腺增生与勃起功能障碍因果关系的孟德尔随机化研究

Mendelian Randomization Study of Causality between Benign Prostatic Hyperplasia and Erectile Dysfunction

摘要: 目的：探讨良性前列腺增生(Benign prostatic hyperplasia, BPH)与勃起功能障碍(Erectile dysfunction, ED)的因果关系。方法：使用公开的BPH及ED全基因组关联研究(Genome-wide association study, GWAS)汇总数据集分别作为暴露因素及结局变量，运用逆方差加权法、简单模式法、加权中值法、加权模式法及MR-Egger法进行两样本孟德尔随机化(Two-sample Mendelian randomization, TSMR)分析。结果：经筛选确定23个单核苷酸多态性(Single nucleotide polymorphism, SNP)作为工具变量，逆方差加权法支持前列腺增生与勃起功能障碍的因果关系(OR and 95% CI: 1.130, 1.014~1.259; p = 0.026)。简单模式法(Simple mode)也显示出相同的因果关系(OR and 95% CI: 1.370, 1.033~1.819; p = 0.040)。MR-Egger：(OR and 95% CI: 1.276, 0.836~1.946; p = 0.271)；加权中位数法：(OR and 95% CI: 1.151, 0.979~1.354; p = 0.090)；加权模式法：(OR and 95% CI: 1.267, 0.989~1.622; p = 0.074)。工具变量之间可认为不存在异质性与水平多效性；使用“留一法”(leave-one-out)进行敏感性分析，因果效应稳健。结论：孟德尔随机化分析结果支持BPH与ED风险增加存在因果关系，为ED的预防和治疗提供了新思路。

Abstract: Objective: To explore the causal relationship between benign prostatic hyperplasia (BPH) and the risk of erectile dysfunction (ED). Methods: The published genome-wide association studies-wide as-sociation study (GWAS) BPH and ED data set were used as the exposure factor andoutcome varia-bles, respectively. Two-sample Mendelian randomization (TSMR) analysis was performed using in-verse variance weighted, simple mode, weighted median, weighted mode methods and MR-Egger regression. Results: Twenty-three SNPs were selected as the instrumental variables, and the in-verse variance weighted method supported the causal relationship between BPH and risk of ED (OR and 95% CI: 1.130, 1.014~1.259; p = 0.026). Simple mode also showed the same causal association (OR and 95% CI: 1.370, 1.033~1.819; p = 0.040). MR-Egger: (OR and 95% CI: 1.276, 0.836~1.946; p = 0.271); Weighted median: (OR and 95% CI: 1.151, 0.979~1.354; p = 0.090); Weighted mode: (OR and 95% CI: 1.267, 0.989~1.622; p = 0.074). It could be considered that there was no heterogeneity and horizontal pleiotropic effect between instrumental variables. The causal effect was robust using the “Leave-one-out” method for sensitivity analysis. Conclusion: Two-sample Mendelian randomiza-tion supports the causal relationship between BPH and increased risk of ED, which provides a new idea for the prevention and treatment of ED.