Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study.
<h4>Aims</h4>To explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as the instrumental variables.<h4>Methods</h4>Genetic loci closely associated with UC were extra...
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2024-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0303827 |
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| author | Xia Wang Tongyi Li Qiu Chen |
| author_facet | Xia Wang Tongyi Li Qiu Chen |
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| description | <h4>Aims</h4>To explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as the instrumental variables.<h4>Methods</h4>Genetic loci closely associated with UC were extracted as instrumental variables and male infertility was the outcome variable in pooled data from the gene-wide association study (GWAS),which was derived from European ethnic groups. The UC data(ebi-a-GCST003045) contained a total sample size of 27432 individuals and 110944 SNPs, and the male infertility data(finn-b-N14_MALEINFERT) contained a total sample size of 73479 individuals and 16377329 SNPs. The SNPs highly correlated with UC were screened from ebi-a-GCST003045(P<5×10-8 as the screening condition, the linkage disequilibrium coefficient was 0.001,and the width of the linkage disequilibrium area was 10000 kb).SNPs related to male infertility from finn-b-N14_MALEINFERT (the minimum r2>0.8,replacing the missing SNPs with SNPs with high linkage, and deleting SNPs without substitution sites) were extracted. MR analysis was performed using MR-Egger regression, the weighted median and the inverse-variance weighted (IVW) respectively, and the causal relationship between UC and male infertility was evaluated by OR and 95% CI, and the Egger-intercept method was used to test for horizontal multiplicity, and the sensitivity analysis was performed using "leave-one-out method". Finally, we used Bayesian Weighted Mendelian Randomization (BWMR) approach to test the results of MR study.<h4>Results</h4>A total of 86 SNPs were included as IVs, with OR and 95% CI of 1.095(0.820~1.462)、1.059(0.899~1.248)、1.125(1.002~1.264) for MR-Egger, the weighted median and IVW results respectively, and P value of less than 0.05 for IVW, indicating that a causal relationship between UC and male infertility was causally related. The results of MR analysis combined with BWMR analysis also showed positive genetic causal relationship between UC and male infertility.MR-Egger regression showed an intercept of -2.21×10-3 with a standard error of 0.006 and P = 0.751, there was no horizontal pleiotropy for the IVs of exposure factors. Heterogeneity tests showed no heterogeneity and the results of the "leave-one-out" sensitivity analysis were stable.<h4>Conclusion</h4>There is a causal association between UC and male infertility, which increases the risk of developing male infertility. |
| format | Article |
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| spelling | doaj-art-7896ae65d67c46e888dfd1109daa87c62025-01-17T05:32:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01195e030382710.1371/journal.pone.0303827Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study.Xia WangTongyi LiQiu Chen<h4>Aims</h4>To explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as the instrumental variables.<h4>Methods</h4>Genetic loci closely associated with UC were extracted as instrumental variables and male infertility was the outcome variable in pooled data from the gene-wide association study (GWAS),which was derived from European ethnic groups. The UC data(ebi-a-GCST003045) contained a total sample size of 27432 individuals and 110944 SNPs, and the male infertility data(finn-b-N14_MALEINFERT) contained a total sample size of 73479 individuals and 16377329 SNPs. The SNPs highly correlated with UC were screened from ebi-a-GCST003045(P<5×10-8 as the screening condition, the linkage disequilibrium coefficient was 0.001,and the width of the linkage disequilibrium area was 10000 kb).SNPs related to male infertility from finn-b-N14_MALEINFERT (the minimum r2>0.8,replacing the missing SNPs with SNPs with high linkage, and deleting SNPs without substitution sites) were extracted. MR analysis was performed using MR-Egger regression, the weighted median and the inverse-variance weighted (IVW) respectively, and the causal relationship between UC and male infertility was evaluated by OR and 95% CI, and the Egger-intercept method was used to test for horizontal multiplicity, and the sensitivity analysis was performed using "leave-one-out method". Finally, we used Bayesian Weighted Mendelian Randomization (BWMR) approach to test the results of MR study.<h4>Results</h4>A total of 86 SNPs were included as IVs, with OR and 95% CI of 1.095(0.820~1.462)、1.059(0.899~1.248)、1.125(1.002~1.264) for MR-Egger, the weighted median and IVW results respectively, and P value of less than 0.05 for IVW, indicating that a causal relationship between UC and male infertility was causally related. The results of MR analysis combined with BWMR analysis also showed positive genetic causal relationship between UC and male infertility.MR-Egger regression showed an intercept of -2.21×10-3 with a standard error of 0.006 and P = 0.751, there was no horizontal pleiotropy for the IVs of exposure factors. Heterogeneity tests showed no heterogeneity and the results of the "leave-one-out" sensitivity analysis were stable.<h4>Conclusion</h4>There is a causal association between UC and male infertility, which increases the risk of developing male infertility.https://doi.org/10.1371/journal.pone.0303827 |
| spellingShingle | Xia Wang Tongyi Li Qiu Chen Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. PLoS ONE |
| title | Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. |
| title_full | Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. |
| title_fullStr | Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. |
| title_full_unstemmed | Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. |
| title_short | Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. |
| title_sort | causal relationship between ulcerative colitis and male infertility a two sample mendelian randomization study |
| url | https://doi.org/10.1371/journal.pone.0303827 |
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