TY - JOUR
T1 - Branched-chain amino acids levels associated with risk of erectile dysfunction
T2 - A Mendelian randomization analysis
AU - Deng, Yijian
AU - Zeng, Liying
AU - Lai, Yigui
AU - Ji, Shuai
AU - Peng, Baizhao
AU - Lu, Hanqi
AU - Wang, Ming
AU - Kwan, Hiu Yee
AU - Wang, Qi
AU - Zhao, Xiaoshan
N1 - Funding Information:
This work was supported by Guangzhou Science and Technology Plan Project (2024B03J1343), the Major scientific and technological project of Guangzhou Municipal Health Commission (20252D003), the Scientific Research Fund of Yangjiang People's Hospital (G2021002), open Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine, and the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (SZ2021KF12), Guangdong Provincial Basic and Applied Basic Research Funding Committee, Regional Joint Fund-Regional Cultivation Program (2022A1515140140), and Dongguan Social Science and Technology Development Key Project (20221800906132).
Publisher Copyright:
© 2025 Published by Elsevier Inc.
PY - 2025/2
Y1 - 2025/2
N2 - Background: Erectile dysfunction (ED) is a prevalent male sexual dysfunction that remarkably impacts patients' quality of life and is also recognized as a precursor to cardiovascular disease (CVD) events. Branched-chain amino acids (BCAAs) are derived from dietary intake and mainly involved in energy metabolism. Previous studies have underscored the association between BCAAs and CVD, but the causal link between BCAAs and ED remains uncertain.Methods: The bidirectional Mendelian randomization (MR) study used the genetic data from genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with total BCAAs, leucine, isoleucine, and valine. The genetic data for ED were acquired from the FinnGen study (n = 95,178). The primary method used to assess causal associations was the inverse variance-weighted (IVW) method, supplemented by MR-Egger, weighted median, and simple median analyses. Cochrane's Q test was utilized to evaluate heterogeneity within the results, while the MR-Egger intercept test was utilized to evaluate the Level pleiotropy. A sensitivity analysis was performed employing leave-one-out analysis.Results: The MR analysis results indicate a positive correlation between levels of total BCAA (OR = 1.984, 95 % CI = 1.018–3.868, P = 0.044), leucine (OR = 2.277, 95 % CI = 1.121–4.626, P = 0.023), isoleucine (OR = 2.584, 95 % CI = 1.167–5.722, P = 0.019), valine (OR = 1.894, 95 % CI = 1.119–3.206, P = 0.017), and the risk of ED. Sensitivity tests confirmed the accuracy and robustness of the study findings. Moreover, the reverse MR analysis found no association between ED and the BCAAs.Conclusion: The results of this analysis indicate a positive association between the circulating BCAA concentrations and the risk of ED, but their underlying mechanisms require further investigation.
AB - Background: Erectile dysfunction (ED) is a prevalent male sexual dysfunction that remarkably impacts patients' quality of life and is also recognized as a precursor to cardiovascular disease (CVD) events. Branched-chain amino acids (BCAAs) are derived from dietary intake and mainly involved in energy metabolism. Previous studies have underscored the association between BCAAs and CVD, but the causal link between BCAAs and ED remains uncertain.Methods: The bidirectional Mendelian randomization (MR) study used the genetic data from genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with total BCAAs, leucine, isoleucine, and valine. The genetic data for ED were acquired from the FinnGen study (n = 95,178). The primary method used to assess causal associations was the inverse variance-weighted (IVW) method, supplemented by MR-Egger, weighted median, and simple median analyses. Cochrane's Q test was utilized to evaluate heterogeneity within the results, while the MR-Egger intercept test was utilized to evaluate the Level pleiotropy. A sensitivity analysis was performed employing leave-one-out analysis.Results: The MR analysis results indicate a positive correlation between levels of total BCAA (OR = 1.984, 95 % CI = 1.018–3.868, P = 0.044), leucine (OR = 2.277, 95 % CI = 1.121–4.626, P = 0.023), isoleucine (OR = 2.584, 95 % CI = 1.167–5.722, P = 0.019), valine (OR = 1.894, 95 % CI = 1.119–3.206, P = 0.017), and the risk of ED. Sensitivity tests confirmed the accuracy and robustness of the study findings. Moreover, the reverse MR analysis found no association between ED and the BCAAs.Conclusion: The results of this analysis indicate a positive association between the circulating BCAA concentrations and the risk of ED, but their underlying mechanisms require further investigation.
KW - Branched-chain amino acid
KW - Erectile dysfunction
KW - GWAS
KW - Mendelian randomization
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85214709857&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2025.112677
DO - 10.1016/j.exger.2025.112677
M3 - Journal article
AN - SCOPUS:85214709857
SN - 0531-5565
VL - 200
JO - Experimental Gerontology
JF - Experimental Gerontology
M1 - 112677
ER -
