Two-sample mendelian randomization analysis based on the GWAS database of type 2 diabetes mellitus and erectile dysfunction

doi:10.3877/cma.j.issn.1674-3253.2026.01.010

Abstract

Abstract:

Objective

Based on the genome-wide association study (GWAS) database, this study utilized R software to explore the causal association between type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED).

Methods

Open genomic data for T2DM (ebi-a-GCST005047) and ED (ebi-a-GCST006956) were downloaded from the GWAS database. After selecting meaningful instrumental variables (IVs), two sample MR analysis was conducted to apply the "TwoSampleMR" package in R software by using inverse variance weighted (IVW), weighted median, MR-Egger regression and weighted mode method.

Results

We selected 24 significant single nucleotide polymorphisms as IVs from the GWAS dataset of T2DM. The IVW results revealed the causal association between T2DM and ED (OR=1.208, 95%CI: 1.088-1.340, P<0.001). The weighted median method provides evidence of a causal association between T2DM and ED (OR=1.254, 95%CI: 1.092-1.441, P=0.001). MR-Egger regression showed that horizontal pleiotropy was unlikely to affect the outcome (P=0.973). The Cochran's Q-test did not show heterogeneity (P>0.05), and the funnel plot did not show asymmetry, further confirming the credibility of the study.

Conclusion

The results of MR analysis support that T2DM may have a causal association with the increased risk of ED.

Key words: GWAS database, Type 2 diabetes mellitus, Erectile dysfunction, Mendelian randomization

Cheng Tang, Genyi Qu, Guang Yang, Yong Xu, Weimin Jiang. Two-sample mendelian randomization analysis based on the GWAS database of type 2 diabetes mellitus and erectile dysfunction[J]. Chinese Journal of Endourology(Electronic Edition), 2026, 20(01): 71-76.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhqjmnmwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3253.2026.01.010

https://zhqjmnmwkzz.cma-cmc.com.cn/EN/Y2026/V20/I01/71

Figures/Tables 8

References 25

[1]	McCabe MP, Sharlip ID, Atalla E, et al. Definitions of sexual dysfunctions in women and men: a consensus statement from the fourth international consultation on sexual medicine 2015[J]. J Sex Med, 2016, 13(2): 135-143. DOI: 10.1016/j.jsxm.2015.12.019.
[2]	Lewis RW, Fugl-Meyer KS, Bosch R, et al. Epidemiology/risk factors of sexual dysfunction[J]. J Sex Med, 2004, 1(1): 35-39. DOI: 10.1111/j.1743-6109.2004.10106.x.
[3]	李健瑛, 李铮, 赵福军. 男性勃起功能障碍的诊疗进展[J]. 临床外科杂志, 2023, 31(2): 117-121. DOI: 10.3969/j.issn.1005-6483.2023.02.006.
[4]	Yang Y, Song Y, Lu Y, et al. Associations between erectile dysfunction and psychological disorders (depression and anxiety): a cross-sectional study in a Chinese population[J]. Andrologia, 2019, 51(10): e13395. DOI: 10.1111/and.13395.
[5]	Ma J, Wan X, Wu B. The cost-effectiveness of lifestyle interventions for preventing diabetes in a health resource-limited setting[J]. J Diabetes Res, 2020, 2020: 7410797. DOI: 10.1155/2020/7410797.
[6]	Mandel N, Büttner M, Poschet G, et al. SUMOylation modulates reactive oxygen species (ROS) levels and acts as a protective mechanism in the type 2 model of diabetic peripheral neuropathy[J]. Cells, 2023, 12(21): 2511. DOI: 10.3390/cells12212511.
[7]	张皓承, 哈小琴. 间充质干细胞对糖尿病合并勃起功能障碍治疗的研究进展[J]. 中国男科学杂志, 2024, 38(2): 149-153. DOI: 10.3969/j.issn.1008-0848.2024.02.025.
[8]	Burgess S, Daniel RM, Butterworth AS, et al. Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways[J]. Int J Epidemiol, 2015, 44(2): 484-495. DOI: 10.1093/ije/dyu176.
[9]	王豪, 许韩峰, 阳源, 等. 两样本孟德尔随机化分析身体质量指数与前列腺癌发病风险的因果关系[J]. 现代泌尿外科杂志, 2024, 29(8): 723-727. DOI: 10.3969/j.issn.1009-8291.2024.08.013.
[10]	Li MJ, Liu Z, Wang P, et al. GWASdb v2: an update database for human genetic variants identified by genome-wide association studies[J]. Nucleic Acids Res, 2016, 44(D1): D869-D876. DOI: 10.1093/nar/gkv1317.
[11]	Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption[J]. Int J Epidemiol, 2017, 46(6): 1985-1998. DOI: 10.1093/ije/dyx102.
[12]	Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression[J]. Int J Epidemiol, 2015, 44(2): 512-525. DOI: 10.1093/ije/dyv080.
[13]	Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in mendelian randomization with some invalid instruments using a weighted Median estimator[J]. Genet Epidemiol, 2016, 40(4): 304-314. DOI: 10.1002/gepi.21965.
[14]	Bowden J, Del Greco M F, Minelli C, et al. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic[J]. Int J Epidemiol, 2016, 45(6): 1961-1974. DOI: 10.1093/ije/dyw220.
[15]	Vicente TFY, Hoai M, Samaras D. Leave-one-out kernel optimization for shadow detection and removal[J]. IEEE Trans Pattern Anal Mach Intell, 2018, 40(3): 682-695. DOI: 10.1109/TPAMI.2017.2691703.
[16]	Rastrelli G, Corona G, Maggi M. Both comorbidity burden and low testosterone can explain symptoms and signs of testosterone deficiency in men consulting for sexual dysfunction[J]. Asian J Androl, 2020, 22(3): 265-273. DOI: 10.4103/aja.aja_61_19.
[17]	Kouidrat Y, Pizzol D, Cosco T, et al. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies[J]. Diabet Med, 2017, 34(9): 1185-1192. DOI: 10.1111/dme.13403.
[18]	Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity[J]. J Clin Endocrinol Metab, 2011, 96(9): 2643-2651. DOI: 10.1210/jc.2010-2724.
[19]	Al-Hunayan A, Al-Mutar M, Kehinde EO, et al. The prevalence and predictors of erectile dysfunction in men with newly diagnosed with type 2 diabetes mellitus[J]. BJU Int, 2007, 99(1): 130-134. DOI: 10.1111/j.1464-410X.2006.06550.x.
[20]	Skeldon SC, Detsky AS, Goldenberg SL, et al. Erectile dysfunction and undiagnosed diabetes, hypertension, and hypercholesterolemia[J]. Ann Fam Med, 2015, 13(4): 331-335. DOI: 10.1370/afm.1816.
[21]	Bovijn J, Jackson L, Censin J, et al. GWAS identifies risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology[J]. Am J Hum Genet, 2019, 104(1): 157-163. DOI: 10.1016/j.ajhg.2018.11.004.
[22]	Schulster ML, Liang SE, Najari BB. Metabolic syndrome and sexual dysfunction[J]. Curr Opin Urol, 2017, 27(5): 435-440. DOI: 10.1097/MOU.0000000000000426.
[23]	Forbes JM, Cooper ME. Mechanisms of diabetic complications[J]. Physiol Rev, 2013, 93(1): 137-188. DOI: 10.1152/physrev.00045.2011.
[24]	Huang PL. A comprehensive definition for metabolic syndrome[J]. Dis Model Mech, 2009, 2(5-6): 231-237. DOI: 10.1242/dmm.001180.
[25]	杨楠惠, 王莹莹, 江叶倩, 等. 2型糖尿病合并高血压男性患者中勃起功能障碍的危险因素分析[J]. 齐齐哈尔医学院学报, 2024, 45(22): 2123-2128. DOI: 10.3969/j.issn.1002-1256.2024.22.005.

SNP	β	SE	P值
rs10842993	0.184800176	0.05484037	0.000752273
rs11257655	0.182922159	0.05483366	0.000850095
rs11708067	0.202734568	0.052842485	0.000124758
rs11709077	0.190579317	0.055659088	0.00061696
rs1215468	0.179892049	0.053830219	0.000832246
rs12571751	0.184967497	0.055348417	0.000832145
rs13266634	0.19705638	0.056333486	0.000468704
rs13293121	0.181565148	0.054357265	0.000837125
rs2237896	0.196741936	0.054706814	0.000322780
rs2261181	0.194896271	0.054155789	0.000319679
rs2290203	0.185450229	0.054736509	0.000703905
rs2383208	0.173212444	0.056396089	0.002130892
rs2972144	0.173026527	0.053323276	0.001175087
rs4481184	0.167187231	0.054338524	0.002092555
rs4580722	0.177890414	0.055014518	0.001222758
rs4719433	0.198030282	0.054125348	0.000253464
rs5015480	0.221979714	0.050650905	0.0000117
rs5215	0.194822759	0.055011372	0.000397859
rs571312	0.184184983	0.054590809	0.000741061
rs6103716	0.189052261	0.054956201	0.00058160
rs6813195	0.199492895	0.053161089	0.000175002
rs7178572	0.173230679	0.052189382	0.000902529
rs864745	0.208129803	0.052495642	0.0000735
rs896854	0.188259913	0.055259415	0.0006572

SNP	β	SE	P值
rs10842993	0.184800176	0.05484037	0.000752273
rs11257655	0.182922159	0.05483366	0.000850095
rs11708067	0.202734568	0.052842485	0.000124758
rs11709077	0.190579317	0.055659088	0.00061696
rs1215468	0.179892049	0.053830219	0.000832246
rs12571751	0.184967497	0.055348417	0.000832145
rs13266634	0.19705638	0.056333486	0.000468704
rs13293121	0.181565148	0.054357265	0.000837125
rs2237896	0.196741936	0.054706814	0.000322780
rs2261181	0.194896271	0.054155789	0.000319679
rs2290203	0.185450229	0.054736509	0.000703905
rs2383208	0.173212444	0.056396089	0.002130892
rs2972144	0.173026527	0.053323276	0.001175087
rs4481184	0.167187231	0.054338524	0.002092555
rs4580722	0.177890414	0.055014518	0.001222758
rs4719433	0.198030282	0.054125348	0.000253464
rs5015480	0.221979714	0.050650905	0.0000117
rs5215	0.194822759	0.055011372	0.000397859
rs571312	0.184184983	0.054590809	0.000741061
rs6103716	0.189052261	0.054956201	0.00058160
rs6813195	0.199492895	0.053161089	0.000175002
rs7178572	0.173230679	0.052189382	0.000902529
rs864745	0.208129803	0.052495642	0.0000735
rs896854	0.188259913	0.055259415	0.0006572

	β	SE	95%CI	OR	P值
MR-Egger	0.196	0.205	0.813~1.818	1.216	0.351
加权中位数	0.226	0.071	1.092~1.441	1.254	0.001
逆方差加权	0.189	0.053	1.088~1.340	1.208	<0.001
加权模式	0.349	0.144	1.069~1.880	1.417	0.024
简单模式	0.352	0.150	1.060~1.907	1.422	0.028

	β	SE	95%CI	OR	P值
MR-Egger	0.196	0.205	0.813~1.818	1.216	0.351
加权中位数	0.226	0.071	1.092~1.441	1.254	0.001
逆方差加权	0.189	0.053	1.088~1.340	1.208	<0.001
加权模式	0.349	0.144	1.069~1.880	1.417	0.024
简单模式	0.352	0.150	1.060~1.907	1.422	0.028

	SNP数量	Cochran's Q	I²	P值
MR-Egger	24	32.35	0.320	0.072
逆方差加权	24	32.35	0.289	0.093

Please choose a citation manager

Content to export