{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:35:46Z","timestamp":1786988146484,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["FG\u20102008\u201036976"],"award-info":[{"award-number":["FG\u20102008\u201036976"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["R1708\u201028972"],"award-info":[{"award-number":["R1708\u201028972"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["TA\u20102204\u201039428"],"award-info":[{"award-number":["TA\u20102204\u201039428"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n In multiple sclerosis, the optimal time for deploying a therapeutic intervention is before the central nervous system is damaged; given the success of trials treating the earliest stage of MS, the radiologically isolated syndrome, developing primary prevention strategies is an important next challenge. To inform this question, we examined the conversion of asymptomatic family members to a diagnosis of MS among Genes and Environment in Multiple Sclerosis (GEMS) project participants. We also evaluated an updated Genetic and Environmental risk score (GERS) and interest in participation in primary prevention trials.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n GEMS is a nationwide prospective study of first\u2010degree relatives of persons with MS; we analyzed data from seven surveys completed over 11\u2009years. 1903 participants completed all questionnaires at study entry. Biological samples were collected in a subset of participants.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among these 1903 first degree relatives, 141 participants had MS at the time of enrollment; 18 participants converted to MS; and 1744 participants did not acquire an MS diagnosis during 8526 person\u2010years of observation. The GERS was significantly higher among participants who had MS at the initial survey than those who did not have an MS diagnosis. The incidence rate of MS was estimated as 211 cases with a 95% confidence interval of 113 to 308 cases per 100,000 first\u2010degree family members per year, which is 100 times greater than the reported incidence of sporadic MS. 48% of the asymptomatic participants were willing to participate in a prevention trial, while 75% expressed willingness when presented with a scenario assuming an elevated risk (20%) of developing MS based on genetic tests performed with blood samples.<\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n Primary prevention trials in MS are urgently needed. Our findings support the feasibility for such studies and inform the design of future primary prevention trials in individuals at risk for MS.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n identifier: NCT01353547\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.70340","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:37:59Z","timestamp":1771331879000},"page":"1591-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Prospective Study of Individuals at Risk of Multiple Sclerosis Informs the Design of Primary Prevention Studies"],"prefix":"10.1002","volume":"13","author":[{"given":"Amy W.","family":"Laitinen","sequence":"first","affiliation":[{"name":"Marcus Neuroscience Institute, Baptist Health South Florida Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceren","family":"Tozlu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Roostaei","sequence":"additional","affiliation":[{"name":"Center for Translational & Computation Neuroimmunology, Columbia Multiple Sclerosis Center, Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatoumata","family":"Diallo","sequence":"additional","affiliation":[{"name":"Center for Translational & Computation Neuroimmunology, Columbia Multiple Sclerosis Center, Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaho","family":"Onomichi","sequence":"additional","affiliation":[{"name":"Center for Translational & Computation Neuroimmunology, Columbia Multiple Sclerosis Center, Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Son","sequence":"additional","affiliation":[{"name":"Center for Translational & Computation Neuroimmunology, Columbia Multiple Sclerosis Center, Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-2589","authenticated-orcid":false,"given":"Zongqi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-2505","authenticated-orcid":false,"given":"Philip L.","family":"De 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