Journal article
A Polymorphism in the HLA-DPB1 Gene Is Associated with Susceptibility to Multiple Sclerosis
PloS one, Vol.5(10), e13454
2010
Abstract
We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.
Details
- Title
- A Polymorphism in the HLA-DPB1 Gene Is Associated with Susceptibility to Multiple Sclerosis
- Authors/Creators
- J. Field (Author/Creator) - Florey Institute of Neuroscience and Mental HealthS.R. Browning (Author/Creator) - University of AucklandL.J. Johnson (Author/Creator) - The University of MelbourneP. Danoy (Author/Creator) - The University of QueenslandM.D. Varney (Author/Creator) - Australian Red Cross LifebloodB.D. Tait (Author/Creator) - Australian Red Cross LifebloodK.S. Gandhi (Author/Creator) - The University of SydneyJ.C. Charlesworth (Author/Creator) - Texas Biomedical Research InstituteR.N. Heard (Author/Creator) - The University of SydneyG.J. Stewart (Author/Creator) - Florey Institute of Neuroscience and Mental HealthT.J. Kilpatrick (Author/Creator) - Menzies Research InstituteS.J. Foote (Author/Creator) - Walter and Eliza Hall Institute of Medical ResearchM. Bahlo (Author/Creator) - Box Hill HospitalH. Butzkueven (Author/Creator) - Florey Institute of Neuroscience and Mental HealthJ. Wiley (Author/Creator) - The University of SydneyD.R. Booth (Author/Creator) - Menzies Research InstituteB.V. Taylor (Author/Creator) - The University of QueenslandM.A. Brown (Author/Creator) - Florey Institute of Neuroscience and Mental HealthJ.P. Rubio (Author/Creator) - Menzies Research InstituteJ. Stankovich (Author/Creator) - University of TasmaniaA.G. Kermode (Author/Creator)
- Publication Details
- PloS one, Vol.5(10), e13454
- Publisher
- Public Library of Science
- Identifiers
- 991005541073007891
- Copyright
- © 2010 Field et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
- Note
- Appears as a member of The Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)
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- Collaboration types
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- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics