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

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  • Bo Li
  • Lingang Zhang
  • Qi Li
  • Jianhua Zhang
  • Wei Wang
  • Jianwen Quan

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.

Suggested Citation

  • Bo Li & Lingang Zhang & Qi Li & Jianhua Zhang & Wei Wang & Jianwen Quan, 2024. "Multiple sclerosis and abnormal spermatozoa: A bidirectional two-sample mendelian randomization study," PLOS ONE, Public Library of Science, vol. 19(8), pages 1-13, August.
    • Handle: RePEc:plo:pone00:0308815
    DOI: 10.1371/journal.pone.0308815
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    References listed on IDEAS

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    1. Zhaotong Lin & Yangqing Deng & Wei Pan, 2021. "Combining the strengths of inverse-variance weighting and Egger regression in Mendelian randomization using a mixture of regressions model," PLOS Genetics, Public Library of Science, vol. 17(11), pages 1-25, November.
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