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A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis

Citation

Field, J and Browning, SR and Johnson, LJ and Danoy, P and Varney, MD and Tait, BD and Gandhi, KS and Charlesworth, JC and Heard, RN and Broadley, SA and Browning, BL and Carroll, WM and Griffiths, LR and Kermode, AG and Lechner-Scott, J and Moscato, P and Perreau, VM and Scott, RJ and Slee, M and Stewart, GJ and Kilpatrick, TJ and Foote, SJ and Bahlo, M and Butzkueven, H and Wiley, J and Booth, DR and Taylor, BV and Brown, MA and Rubio, JP and Stankovich, J, A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis, PLoS ONE, 5, (10) EJ ISSN 1932-6203 (2010) [Refereed Article]


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Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0013454

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 Pƒ4|10{6). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (Pƒ0:001) and were highly significant in the combined dataset (Pƒ6|10{8). 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 P~9|10{9, replication set P~7|10{4, combined P~2|10{10). 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 genomewide 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Preventive Medicine
UTAS Author:Charlesworth, JC (Dr Jac Charlesworth)
UTAS Author:Foote, SJ (Professor Simon Foote)
UTAS Author:Taylor, BV (Professor Bruce Taylor)
UTAS Author:Stankovich, J (Dr Jim Stankovich)
ID Code:66693
Year Published:2010
Web of Science® Times Cited:31
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-02-08
Last Modified:2013-10-21
Downloads:433 View Download Statistics

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