Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 160-167 |
| Number of pages | 8 |
| Journal | American Journal of Human Genetics |
| Volume | 74 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans. / Oksenberg, Jorge R.; Barcellos, Lisa F.; Cree, Bruce A C; Baranzini, Sergio E.; Bugawan, Teodorica L.; Khan, Omar; Lincoln, Robin R.; Swerdlin, Amy; Mignot, Emmanuel; Lin, Ling; Goodin, Douglas; Erlich, Henry A.; Schmidt, Silke; Thomson, Glenys; Reich, David E.; Pericak-Vance, Margaret A; Haines, Jonathan L.; Hauser, Stephen L.
In: American Journal of Human Genetics, Vol. 74, No. 1, 01.01.2004, p. 160-167.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans
AU - Oksenberg, Jorge R.
AU - Barcellos, Lisa F.
AU - Cree, Bruce A C
AU - Baranzini, Sergio E.
AU - Bugawan, Teodorica L.
AU - Khan, Omar
AU - Lincoln, Robin R.
AU - Swerdlin, Amy
AU - Mignot, Emmanuel
AU - Lin, Ling
AU - Goodin, Douglas
AU - Erlich, Henry A.
AU - Schmidt, Silke
AU - Thomson, Glenys
AU - Reich, David E.
AU - Pericak-Vance, Margaret A
AU - Haines, Jonathan L.
AU - Hauser, Stephen L.
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=9144269888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9144269888&partnerID=8YFLogxK
U2 - 10.1086/380997
DO - 10.1086/380997
M3 - Article
C2 - 14669136
AN - SCOPUS:9144269888
VL - 74
SP - 160
EP - 167
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -