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

作者全名：Xiong, Yang; Zhang, Fuxun; Zhang, Yangchang; Wang, Wei; Ran, Yuxin; Wu, Changjing; Zhu, Shiyu; Qin, Feng; Yuan, Jiuhong

作者地址：[Xiong, Yang; Zhang, Fuxun; Wang, Wei; Zhu, Shiyu; Yuan, Jiuhong] Sichuan Univ, West China Hosp, Androl Lab, Chengdu 610041, Peoples R China; [Xiong, Yang; Zhang, Fuxun; Wang, Wei; Wu, Changjing; Zhu, Shiyu; Qin, Feng; Yuan, Jiuhong] Sichuan Univ, West China Hosp, Dept Urol, Chengdu 610041, Peoples R China; [Zhang, Yangchang] Capital Med Univ, Dept Publ Hlth, Beijing 100000, Peoples R China; [Ran, Yuxin] Chongqing Med Univ, Women & Childrens Hosp, Ctr Reprod Med, Chongqing, Peoples R China; [Yuan, Jiuhong] Sichuan Univ, West China Hosp, Dept Urol, Androl Lab, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China

通信作者：Yuan, JH (通讯作者)，Sichuan Univ, West China Hosp, Dept Urol, Androl Lab, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China.

来源：JOURNAL OF ADVANCED RESEARCH

ESI学科分类：Multidisciplinary

WOS号：WOS:001220585600001

JCR分区：Q1

影响因子：11.4

年份：2024

卷号：58

期号：　

开始页：149

结束页：161

文献类型：Article

关键词：Cardiovascular diseases; Erectile dysfunction; Lifestyle factors; Mendelian randomization; Metabolic diseases; Mental disorder

摘要：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. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

基金机构：Natural Science Foundation of China [81871147, 82071639]; Sichuan Science and Technology Program [2022YFS0028, 2022YFS0134]

基金资助正文：The authors sincerely thank the authors who shared the original dataset in this study. This work was supported by the Natural Science Foundation of China (No. 81871147 and No. 82071639) and the Sichuan Science and Technology Program (No. 2022YFS0028 and No. 2022YFS0134) .