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Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were obtained for 1033 self\u2010identified Hispanics with MS from four MS\u2010based registries from four academic institutions across the United States January 2016\u2013April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96\u20130.99; <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>7.80\u00a0\u00d7\u00a010<jats:sup>\u221203<\/jats:sup>) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35\u20134.10; <jats:italic>P<\/jats:italic>\u00a0=\u00a02.60\u00a0\u00d7\u00a010<jats:sup>\u221203<\/jats:sup>). Younger age of onset was found to be associated with a higher proportion NA (Beta: \u22125.58; <jats:italic>P<\/jats:italic>\u00a0=\u00a03.49\u00a0\u00d7\u00a010<jats:sup>\u221202<\/jats:sup>) and African ancestry (Beta: \u221210.07; <jats:italic>P<\/jats:italic>\u00a0=\u00a01.39\u00a0\u00d7\u00a010<jats:sup>\u221203<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.646","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T06:59:06Z","timestamp":1537772346000},"page":"1362-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis"],"prefix":"10.1002","volume":"5","author":[{"given":"Lilyana","family":"Amezcua","sequence":"first","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley H.","family":"Beecham","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Department of Human Genetics Miller School of Medicine University of Miami Miami Florida"},{"name":"John P. Hussman Institute of Human Genomics Miller School of Medicine University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia R.","family":"Delgado","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Division Department of Neurology Miller School of Medicine University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"Chinea","sequence":"additional","affiliation":[{"name":"San Juan Multiple Sclerosis Center San Juan Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara Patricia","family":"Manrique","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute of Human Genomics Miller School of Medicine University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Refujia","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Comabella","sequence":"additional","affiliation":[{"name":"Department of Neurology University of San Francisco School of Medicine Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Montalban","sequence":"additional","affiliation":[{"name":"Department of Neurology University of San Francisco School of Medicine Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Ortega","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Division Department of Neurology Miller School of Medicine University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia","family":"Tornes","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Division Department of Neurology Miller School of Medicine University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett T.","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talat","family":"Islam","sequence":"additional","affiliation":[{"name":"Department de Neurolog\u00eda\u2010Neuroinmunolog\u00eda Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat) Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Conti","sequence":"additional","affiliation":[{"name":"Department de Neurolog\u00eda\u2010Neuroinmunolog\u00eda Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat) Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge R.","family":"Oksenberg","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob L.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Dr. John T. 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