Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Autor:	Jiang Y; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Cesta CE; Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden., Liu Q; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Kingwell E; Research Department of Primary Care & Population Health, University College London, London, UK., Stridh P; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Shchetynsky K; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Olsson T; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Kockum I; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Stener-Victorin E; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Jiang X; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Manouchehrinia A; Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2024 Dec; Vol. 30 (14), pp. 1765-1774. Date of Electronic Publication: 2024 Nov 06.
DOI:	10.1177/13524585241292802
Abstrakt:	Background: Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk. Objective: To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis. Methods: Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture. Results: In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS ( HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p -values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS. Conclusion: We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights. Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu