基于GWAS数据库的2型糖尿病与勃起功能障碍两样本孟德尔随机化分析

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

目的

本研究基于全基因组关联研究（GWAS）数据库平台，使用R语言软件利用孟德尔随机化（MR）方法探讨2型糖尿病（T2DM）与勃起功能障碍（ED）之间的因果关系。

方法

从GWAS数据库平台下载开放的T2DM（ebi-a-GCST005047）和ED（ebi-a-GCST006956）基因组数据，筛选出有意义的工具变量（IVs），并通过R语言中的"TwoSampleMR"包采用逆方差加权（IVW）、加权中位数、MR-Egger回归和加权众数法进行两样本MR分析。

结果

从T2DM的GWAS数据集中筛选出24个显著的单核苷酸多态性作为IVs。IVW分析结果显示，T2DM和ED之间存在因果关系（OR=1.208，95%CI：1.088~1.340，P<0.001）。加权中位数方法则提供了T2DM与ED之间存在因果关系的证据（OR=1.254，95%CI：1.092~1.441，P=0.001）。MR-Egger回归分析结果显示，水平多效性对结果无显著影响（P=0.973）。Cochran's Q检验未显示异质性（P>0.05），漏斗图也未显示出不对称性，进一步证实了研究结果的可靠性。

结论

MR分析结果支持2型糖尿病可能与ED风险增加有因果关系。

关键词: 全基因组关联研究数据库, 2型糖尿病, 勃起功能障碍, 孟德尔随机化

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

图1 两样本孟德尔随机化（MR）分析流程图

图2 与T2DM指数相关的SNP对ED因果效应的森林图注：红色点线的意义为MR-Egger分析和逆方差加权（IVW）法的MR结果

表1 T2DM与ED相关的24个SNP特征

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

表1 T2DM与ED相关的24个SNP特征

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

图3 T2DM相关的SNP与ED相关的SNP关联性散点图

表2 T2DM和ED之间的因果效应MR分析结果

	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

表2 T2DM和ED之间的因果效应MR分析结果

	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

图4 T2DM与ED风险相关的"留一法"分析

图5 评估MR异质性的漏斗图

表3 使用MR方法对T2DM及ED的异质性分析结果

	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

表3 使用MR方法对T2DM及ED的异质性分析结果

	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

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

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