Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS.

Autor:	Gianfrancesco MA; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Stridh P; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Rhead B; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Shao X; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Xu E; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Graves JS; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Chitnis T; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Waldman A; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Lotze T; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Schreiner T; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Belman A; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Greenberg B; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Weinstock-Guttman B; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Aaen G; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Tillema JM; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Hart J; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Caillier S; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Ness J; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Harris Y; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Rubin J; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Candee M; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Krupp L; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Gorman M; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Benson L; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Rodriguez M; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Mar S; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Kahn I; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Rose J; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Roalstad S; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Casper TC; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Shen L; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Quach H; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Quach D; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Hillert J; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Bäärnhielm M; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Hedstrom A; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Olsson T; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Kockum I; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Alfredsson L; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Metayer C; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Schaefer C; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Barcellos LF; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA., Waubant E; From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA. emmanuelle.waubant@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2017 Apr 25; Vol. 88 (17), pp. 1623-1629. Date of Electronic Publication: 2017 Mar 29.
DOI:	10.1212/WNL.0000000000003849
Abstrakt:	Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10,875 controls) and Sweden (n = 175 cases, 5,376 controls; total n = 16,820). Results: Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01 , and over 100 non-human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model. Conclusions: We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS. (© 2017 American Academy of Neurology.)
Databáze:	MEDLINE
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