Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 74, Issue 1, Pages 160-167Publisher
CELL PRESS
DOI: 10.1086/380997
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM035326] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS026799, R01NS046297] Funding Source: NIH RePORTER
- NIGMS NIH HHS [R01 GM035326, GM35326] Funding Source: Medline
- NINDS NIH HHS [NS 26799, NS 46297, R01 NS026799, R01 NS046297] Funding Source: Medline
- CSR NIH HHS [RG3060] Funding Source: Medline
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An underlying complex genetic susceptibility exists in multiple sclerosis ( MS), and an association with the HLA-DRB1* 1501-DQB1* 0602 haplotype has been repeatedly demonstrated in high-risk ( northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1* 15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.
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