{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:42:14Z","timestamp":1786326134041,"version":"build-2736575974"},"reference-count":25,"publisher":"SAGE Publications","issue":"14","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"crossref","award":["2-1534\/2020"],"award-info":[{"award-number":["2-1534\/2020"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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\u20131.15), 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 &gt; 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585241292802","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T07:12:43Z","timestamp":1730877163000},"page":"1765-1774","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4542-9578","authenticated-orcid":false,"given":"Yuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn E","family":"Cesta","sequence":"additional","affiliation":[{"name":"Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-1700","authenticated-orcid":false,"given":"Elaine","family":"Kingwell","sequence":"additional","affiliation":[{"name":"Research Department of Primary Care & Population Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-0039","authenticated-orcid":false,"given":"Pernilla","family":"Stridh","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klementy","family":"Shchetynsky","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-4726","authenticated-orcid":false,"given":"Ingrid","family":"Kockum","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Stener-Victorin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, 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