Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study.

Area of Science:

• Genetics
• Gastroenterology
• Reproductive Medicine

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease.
• Male infertility is a significant global health concern.
• The relationship between UC and male infertility requires further investigation.

Purpose of the Study:

• To investigate the potential causal relationship between ulcerative colitis (UC) and male infertility.
• Utilize Mendelian randomization (MR) with single nucleotide polymorphisms (SNPs) as instrumental variables.
• Assess genetic predisposition from large-scale genome-wide association studies (GWAS).

Main Methods:

• Employed Mendelian randomization (MR) analysis using summary statistics from GWAS data.
• Selected 86 SNPs strongly associated with UC as instrumental variables.
• Applied MR-Egger, weighted median, and inverse-variance weighted (IVW) methods, with Bayesian Weighted Mendelian Randomization (BWMR) for validation.

Main Results:

• The IVW analysis indicated a significant causal effect of UC on male infertility (P < 0.05).
• MR-Egger regression and BWMR analysis corroborated a positive genetic causal relationship.
• Sensitivity analyses, including heterogeneity and pleiotropy tests, confirmed the robustness of the findings.

Conclusions:

• Ulcerative colitis (UC) is causally associated with an increased risk of male infertility.
• This finding suggests a potential biological link influencing male reproductive health in UC patients.
• Further research may explore underlying mechanisms and therapeutic targets.