{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:36:58Z","timestamp":1787503018019,"version":"build-2736575974"},"reference-count":44,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants\u2019 risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585241257205","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T08:13:05Z","timestamp":1717747985000},"page":"994-1003","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-1938","authenticated-orcid":false,"given":"Andrea","family":"Nova","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1913-9897","authenticated-orcid":false,"given":"Giovanni","family":"Di Caprio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bernardinelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-8450","authenticated-orcid":false,"given":"Teresa","family":"Fazia","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"bibr1-13524585241257205","volume":"4","author":"Kuhlmann T","year":"2023","journal-title":"Free Neuropathol"},{"key":"bibr2-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58649"},{"key":"bibr3-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50862"},{"key":"bibr4-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11072-4"},{"key":"bibr5-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517732841"},{"key":"bibr6-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028944"},{"issue":"6460","key":"bibr7-13524585241257205","volume":"365","author":"Patsopoulos NA","year":"2019","journal-title":"Science"},{"key":"bibr8-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2770"},{"key":"bibr9-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"bibr10-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16088"},{"key":"bibr11-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32885-x"},{"key":"bibr12-13524585241257205","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"bibr13-13524585241257205","unstructured":"Thompson DJ, Wells D, Selzam S, et al. 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