Multiple sclerosis and abnormal spermatozoa: A bidirectional two-sample mendelian randomization study

PLoS One. 2024 Aug 20;19(8):e0308815. doi: 10.1371/journal.pone.0308815. eCollection 2024.

Abstract

Objective: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and previous observational epidemiological studies have suggested an association between MS and male infertility; male infertility due to sperm abnormalities may result from a number of aetiological factors, such as genetics, autoimmune factors, etc., and there are currently no studies to assess whether MS is associated with sperm abnormalities in men. Therefore, we performed a Mendelian randomization (MR) analysis to assess the causal relationship between MS and abnormal spermatozoa.

Methods: In this study, independent single nucleotide polymorphisms (SNPs) strongly associated with multiple sclerosis (MS) were identified by mining public genome-wide association study repositories and used as instrumental variables to explore causality. The causal effect of MS on sperm abnormalities was systematically assessed using two-sample Mendelian randomization (MR) techniques, and various analytical models such as inverse variance weighting (IVW), MR-Egger and MR-PRESSO were implemented to dissect the association. In addition, a wide range of sensitivity tests, including Cochran's Q test to detect heterogeneity, MR-Egger intercept analysis to assess bias, leave-one-out to test model robustness, and funnel plot analysis to detect potential publication bias, were implemented to ensure the robustness and reliability of the causal inference results.

Results: There was a significant causal relationship between MS and abnormal sperm (OR 1.090, 95% CI [1.017-1.168], p = 0.014); The accuracy and robustness of the results were confirmed by sensitivity analysis.

Conclusion: Here we show that there appears to be a causal relationship between multiple sclerosis and abnormal spermatozoa. MS as a chronic disease has a higher risk of concomitant sperm abnormalities in its male patients, and reproductive and fertility issues in men with MS should receive special attention from clinicians.

MeSH terms

  • Genome-Wide Association Study*
  • Humans
  • Infertility, Male / genetics
  • Male
  • Mendelian Randomization Analysis*
  • Multiple Sclerosis* / genetics
  • Polymorphism, Single Nucleotide*
  • Spermatozoa* / metabolism
  • Spermatozoa* / pathology

Grants and funding

This study was supported by the Project Fund of Basic Research Programme of Yuncheng City, Shanxi Province, China (Project No. YCKJ-2023052 to L.Z.)