Using a two sample Mendelian randomization approach to explore the causal relationship between erectile dysfunction and lung function

Yurui Luo; Shiqi Su; Yong Yang; Nanyan Xiang; Tingting Fu; Su Lui; Yifei Lin; Jin Huang

doi:10.21037/tau-24-321

Using a two sample Mendelian randomization approach to explore the causal relationship between erectile dysfunction and lung function

Transl Androl Urol. 2024 Nov 30;13(11):2439-2447. doi: 10.21037/tau-24-321. Epub 2024 Nov 28.

Authors

Yurui Luo^#¹, Shiqi Su^#¹, Yong Yang², Nanyan Xiang¹, Tingting Fu³, Su Lui⁴, Yifei Lin^{5

6}, Jin Huang⁵

Affiliations

¹ Department of Urology, Innovation Institute for Integration of Medicine and Engineering, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
² Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Urology, Innovation Institute for Integration of Medicine and Engineering, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, and Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
⁴ Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
⁵ Department of Urology, Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China.
⁶ Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

^# Contributed equally.

Abstract

Background: Recently, some observational studies have suggested potential associations between erectile dysfunction (ED) and respiratory function. However, the underlying biological mechanisms and causal relationships between ED and lung function require further investigation. This study aimed to explore the causalities between ED and lung function traits.

Methods: Single-nucleotide polymorphisms (SNPs) for ED were extracted from the Finngen_r7 (1,154 cases and 94,024 controls), and the summary statistics of respiratory function were extracted from the UK Biobank (UKB) (n=321,047). We utilized several Mendelian randomization (MR) methods to mitigate the impact of weak instrument bias and pleiotropy. To address potential confounding effects, multivariable MR (MVMR) analyses were also conducted, adjusting for demographic factors and respiratory conditions. Moreover, recently developed latent causal variable (LCV) modeling was also performed to enhance the robustness of the findings.

Results: Totally 15 SNPs robustly associated with ED were included. We found that higher risk of ED was associated with decreased of forced expiratory volume in the first second (FEV1) [odds ratio (OR) 0.992, 95% confidence interval (CI): 0.986, 0.997, P=0.003], as was the case for forced vital capacity (FVC) (OR 0.994, 95% CI: 0.989, 1.000, P=0.04), peak expiratory flow (PEF) (OR 0.990, 95% CI: 0.990, 0.990, P=0.01) and FEV1/FVC ratio (OR 0.991, 95% CI: 0.985, 0.997, P=0.002). After adjusting for confounding factors, ED only demonstrated causal effects on FEV1/FVC ratio. Notably, the LCV analysis provided additional support for the positive causal impact of ED on FEV1 and FVC. Conversely, reverse MR analysis did not reveal compelling evidence for a causal effect of lung function on ED.

Conclusions: Our study suggests a potential causal relationship between higher ED susceptibility and reduced respiratory function, as indicated by decreased FEV1, FVC, PEF, and the FEV1/FVC ratio. The results enhanced understanding of the intricate interrelationships between ED and lung function.

Keywords: Mendelian randomization (MR); causal relationship; erectile dysfunction (ED); genetic epidemiology; lung function.