Type 2 diabetes mellitus and the risk of male infertility: a Mendelian randomization study
To assess the causal effect of type 2 diabetes mellitus (T2DM) on male infertility (MI) and erectile dysfunction (ED) by Mendelian randomization (MR) analysis. Data for T2DM, MI, and ED were obtained from genome-wide association studies (GWAS) involving 298, 957, 73, 479, and 223, 805 Europeans, res...
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Published in | Frontiers in endocrinology (Lausanne) Vol. 14; p. 1279058 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
12.12.2023
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Subjects | |
Online Access | Get full text |
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Summary: | To assess the causal effect of type 2 diabetes mellitus (T2DM) on male infertility (MI) and erectile dysfunction (ED) by Mendelian randomization (MR) analysis.
Data for T2DM, MI, and ED were obtained from genome-wide association studies (GWAS) involving 298, 957, 73, 479, and 223, 805 Europeans, respectively. We performed univariate MR analysis using MR Egger, Weighted median (WM) and Inverse variance weighted (IVW) methods to assess causal effects among the three. Through the Genotype Tissue Expression (GTEx) database, single-nucleotide polymorphisms (SNPs) that affect the expression levels of T2DM-related genes were located using expression quantitative trait loci (eQTL).
MR analysis showed a significant causal relationship between T2DM and ED (WM, OR: 1.180, 95%CI: 1.010-1.378,
= 0.037; IVW, OR: 1.190, 95%CI: 1.084-1.300,
< 0.001). There is also a significant causal relationship between T2DM and MI (MR Egger, OR: 0.549, 95%CI: 0.317-0.952,
= 0.037; WM, OR: 0.593, 95%CI: 0.400,
= 0.010; IVW, OR: 0.767, 95%CI: 0.600-0.980,
= 0.034). ED may not cause MI (
> 0.05). We also found that rs6585827 corresponding to the PLEKHA1 gene associated with T2DM is an eQTL variant affecting the expression of this gene.
T2DM has a direct causal effect on ED and MI. The level of PLEKHA1 expression suppressed by rs6585827 is potentially associated with a lower risk of T2DM. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Xiaoling Li, University of Texas Southwestern Medical Center, United States Edited by: Kai Guo, University of Michigan, United States Reviewed by: Hongyao Xie, Eli Lilly, United States |
ISSN: | 1664-2392 1664-2392 |
DOI: | 10.3389/fendo.2023.1279058 |