洞悉可调节的勃起功能障碍风险因素：一项广角孟德尔随机化研究。

Insights into modifiable risk factors of erectile dysfunction, a wide-angled Mendelian Randomization study.

机构信息

Andrology Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Public Health, Capital Medical University, Beijing 100000, China.

出版信息

J Adv Res. 2024 Apr;58:149-161. doi: 10.1016/j.jare.2023.05.008. Epub 2023 May 25.

DOI:10.1016/j.jare.2023.05.008

PMID:37236543

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10982860/

Abstract

INTRODUCTION

The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED.

METHODS

Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings.

RESULTS

Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05).

CONCLUSION

This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.

摘要

简介

可改变的风险因素与勃起功能障碍（ED）之间的因果关系仍不清楚，这阻碍了 ED 患者的早期识别和干预。本研究旨在阐明 42 种主要风险因素与 ED 之间的因果关系。

方法

采用单变量 Mendelian Randomization（MR）、多变量 MR 和中介 MR 分析来研究 42 种可改变的风险因素与 ED 之间的因果关系。使用来自两项独立 ED 全基因组关联研究的合并结果来验证研究结果。

结果

遗传预测的体重指数（BMI）、腰围、躯干脂肪量、全身脂肪量、整体健康状况不佳、2 型糖尿病、基础代谢率、脂联素、吸烟、失眠、打鼾、高血压、中风、缺血性中风、冠心病、心肌梗死、心力衰竭和重度抑郁症与 ED 风险增加相关（均 P<0.05）。此外，较高的体脂百分比和酒精摄入量的遗传倾向与 ED 风险增加呈提示性相关（P<0.05 和调整后 P>0.05）。遗传易感性导致较高的性激素结合球蛋白（SHBG）水平可降低 ED 风险（P<0.05）。血脂水平与 ED 之间无显著相关性。多变量 MR 确定 2 型糖尿病、基础代谢率、吸烟、高血压和冠心病为 ED 的危险因素。合并结果证实，腰围、全身脂肪量、整体健康状况不佳、2 型糖尿病、基础代谢率、脂联素、吸烟、打鼾、高血压、缺血性中风、冠心病、心肌梗死、心力衰竭和重度抑郁症可增加 ED 风险（均 P<0.05），而较高的 SHBG 降低 ED 风险（P=0.004）。BMI、失眠和中风对 ED 有提示性意义（P<0.05 和调整后 P>0.05）。