Genetic prediction of modifiable lifestyle factors for erectile dysfunction

Yu-Jia Xi; Yi-Ge Feng; Ya-Qi Bai; Rui Wen; He-Yi Zhang; Qin-Yi Su; Qiang Guo; Cheng-Yong Li; Zhen-Xing Wang; Liang Pei; Sheng-Xiao Zhang; Jing-Qi Wang

doi:10.1093/sexmed/qfae010

Genetic prediction of modifiable lifestyle factors for erectile dysfunction

Sex Med. 2024 Mar 18;12(1):qfae010. doi: 10.1093/sexmed/qfae010. eCollection 2024 Feb.

Authors

Yu-Jia Xi^{1

2

3}, Yi-Ge Feng^{2

3}, Ya-Qi Bai^{2

3}, Rui Wen^{2

3}, He-Yi Zhang^{2

3}, Qin-Yi Su^{1

2

3}, Qiang Guo¹, Cheng-Yong Li¹, Zhen-Xing Wang¹, Liang Pei¹, Sheng-Xiao Zhang^{2

3

4}, Jing-Qi Wang¹

Affiliations

¹ Department of Urology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
² Shanxi Provincial Key Laboratory of Rheumatism Immune Microecology, Taiyuan, Shanxi Province 030001, China.
³ Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi Province 030001, China.
⁴ Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Abstract

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain.

Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR).

Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED.

Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED.

Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10^-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked.

Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED.

Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry.

Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.

Keywords: Mendelian randomization; causal effect; erectile dysfunction; genome-wide association; lifestyle factors.