Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.
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Christen, U., von Herrath, M. G.
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Bager, P., Nielsen, N. M., Bihrmann, K., Frisch, M., Hjalgrim, H., Wohlfart, J., Koch-Henriksen, N., Melbye, M., Westergaard, T.
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[Abstract][Full Text]
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(2003). New Loci Regulating Rat Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis. J. Immunol.
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[Abstract][Full Text]
Dyment, D. A., Cader, M. Z., Willer, C. J., Risch, N., Sadovnick, A. D., Ebers, G. C.
(2002). A multigenerational family with multiple sclerosis. Brain
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[Abstract][Full Text]
Sawcer, S., Maranian, M., Setakis, E., Curwen, V., Akesson, E., Hensiek, A., Coraddu, F., Roxburgh, R., Sawcer, D., Gray, J., Deans, J., Goodfellow, P. N., Walker, N., Clayton, D., Compston, A.
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125: 1337-1347
[Abstract][Full Text]
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(2002). Linkage analysis conditional on HLA status in a large North American pedigree supports the presence of a multiple sclerosis susceptibility locus on chromosome 12p12. Hum Mol Genet
11: 295-300
[Abstract][Full Text]
Siger-Zajdel, M., Filippi, M., Selmaj, K.
(2002). MTR discloses subtle changes in the normal-appearing tissue from relatives of patients with MS. Neurology
58: 317-320
[Abstract][Full Text]
Siger-Zajdel, M, Selmaj, K
(2001). Magnetisation transfer ratio analysis of normal appearing white matter in patients with familial and sporadic multiple sclerosis. J. Neurol. Neurosurg. Psychiatry
71: 752-756
[Abstract][Full Text]
Mirsattari, S.M., Johnston, J.B., McKenna, R., Del Bigio, M.R., Orr, P., Ross, R.T., Power, C.
(2001). Aboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica. Neurology
56: 317-323
[Abstract][Full Text]
The Transatlantic Multiple Sclerosis Genetics Coop,
(2001). A meta-analysis of genomic screens in multiple sclerosis. Mult Scler
7: 3-11
[Abstract]
Alvarado-de la Barrera, C., Zuniga-Ramos, J., Ruiz-Morales, J. A., Estanol, B., Granados, J., Llorente, L.
(2000). HLA class II genotypes in Mexican Mestizos with familial and nonfamilial multiple sclerosis. Neurology
55: 1897-1900
[Abstract][Full Text]
Johnson, M R, Ferner, R E, Bobrow, M, Hughes, R A C
(2000). Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis. J. Neurol. Neurosurg. Psychiatry
68: 643-646
[Abstract][Full Text]
Coffeen, C. M., McKenna, C. E., Koeppen, A. H., Plaster, N. M., Maragakis, N., Mihalopoulos, J., Schwankhaus, J. D., Flanigan, K. M., Gregg, R. G., Ptacek, L. J., Fu, Y.-H.
(2000). Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31. Hum Mol Genet
9: 787-793
[Abstract][Full Text]
Ebers, G. C., Koopman, W. J., Hader, W., Sadovnick, A. D., Kremenchutzky, M., Mandalfino, P., Wingerchuk, D. M., Baskerville, J., Rice, G. P. A.
(2000). The natural history of multiple sclerosis: a geographically based study: 8: Familial multiple sclerosis. Brain
123: 641-649
[Abstract][Full Text]
Holz, A., Bielekova, B., Martin, R., Oldstone, M. B. A.
(2000). Myelin-Associated Oligodendrocytic Basic Protein: Identification of an Encephalitogenic Epitope and Association with Multiple Sclerosis. J. Immunol.
164: 1103-1109
[Abstract][Full Text]
Aubagnac, S., Brahic, M., Bureau, J.-F.
(1999). Viral Load and a Locus on Chromosome 11 Affect the Late Clinical Disease Caused by Theiler's Virus. J. Virol.
73: 7965-7971
[Abstract][Full Text]
Haegert, D. G., Cowan, T., Murray, T. J., Gadag, V., O'Connor, P.
(1999). Does a shift in the T-cell receptor repertoire precede the onset of MS?. Neurology
53: 485-485
[Abstract][Full Text]
Fulton, J. C, Grossman, R. I, Mannon, L. J, Udupa, J., Kolson, D. L
(1999). Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals. Mult Scler
5: 74-77
[Abstract]
Goodin, D. S, Northern California MS Study Group,
(1999). Survey of multiple sclerosis in Northern California. Mult Scler
5: 78-88
[Abstract]
Dahlman, I., Jacobsson, L., Glaser, A., Lorentzen, J. C., Andersson, M., Luthman, H., Olsson, T.
(1999). Genome-Wide Linkage Analysis of Chronic Relapsing Experimental Autoimmune Encephalomyelitis in the Rat Identifies a Major Susceptibility Locus on Chromosome 9. J. Immunol.
162: 2581-2588
[Abstract][Full Text]
Oldstone, M. B. A.
(1998). Molecular mimicry and immune-mediated diseases. FASEB J.
12: 1255-1265
[Abstract][Full Text]
Weissert, R., Svenningsson, A., Lobell, A., de Graaf, K. L., Andersson, R., Olsson, T.
(1998). Molecular and Genetic Requirements for Preferential Recruitment of TCRBV8S2+ T Cells in Lewis Rat Experimental Autoimmune Encephalomyelitis. J. Immunol.
160: 681-690
[Abstract][Full Text]
Falcone, M., Bloom, B. R.
(1997). A T Helper Cell 2 (Th2) Immune Response against Non-self Antigens Modifies the Cytokine Profile of Autoimmune T Cells and Protects against Experimental Allergic Encephalomyelitis. JEM
185: 901-908
[Abstract][Full Text]
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