Jiang, Yuan;
Cesta, Carolyn E;
Liu, Qianwen;
Kingwell, Elaine;
Stridh, Pernilla;
Shchetynsky, Klementy;
Olsson, Tomas;
... Manouchehrinia, Ali; + view all
(2024)
Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.
Multiple Sclerosis Journal
, 30
(14)
pp. 1765-1774.
10.1177/13524585241292802.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1177/13524585241292802 |
| Publisher version: | https://doi.org/10.1177/13524585241292802 |
| Language: | English |
| Additional information: | © The Author(s) 2024. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Polycystic ovary syndrome sex hormone multiple sclerosis cohort study genome-wide cross-trait analysis genomics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10205754 |
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