PMID- 21049023
OWN - NLM
STAT- MEDLINE
DCOM- 20110307
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 10
DP  - 2010 Oct 26
TI  - A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple 
      sclerosis.
PG  - e13454
LID - 10.1371/journal.pone.0013454 [doi]
LID - e13454
AB  - 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 P 
      </= 4 x 10(-6)). All associations were significant in an independent replication 
      cohort of 2212 cases and 2251 controls (P </= 0.001) and were highly significant in 
      the combined dataset (P </= 6 x 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 x 
      10(-9), replication set P = 7 x 10(-4), combined P = 2 x 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 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.
FAU - Field, Judith
AU  - Field J
AD  - Florey Neuroscience Institutes, University of Melbourne, Melbourne, Victoria, 
      Australia.
FAU - Browning, Sharon R
AU  - Browning SR
FAU - Johnson, Laura J
AU  - Johnson LJ
FAU - Danoy, Patrick
AU  - Danoy P
FAU - Varney, Michael D
AU  - Varney MD
FAU - Tait, Brian D
AU  - Tait BD
FAU - Gandhi, Kaushal S
AU  - Gandhi KS
FAU - Charlesworth, Jac C
AU  - Charlesworth JC
FAU - Heard, Robert N
AU  - Heard RN
CN  - Australia and New Zealand Multiple Sclerosis Genetics Consortium
FAU - Stewart, Graeme J
AU  - Stewart GJ
FAU - Kilpatrick, Trevor J
AU  - Kilpatrick TJ
FAU - Foote, Simon J
AU  - Foote SJ
FAU - Bahlo, Melanie
AU  - Bahlo M
FAU - Butzkueven, Helmut
AU  - Butzkueven H
FAU - Wiley, James
AU  - Wiley J
FAU - Booth, David R
AU  - Booth DR
FAU - Taylor, Bruce V
AU  - Taylor BV
FAU - Brown, Matthew A
AU  - Brown MA
FAU - Rubio, Justin P
AU  - Rubio JP
FAU - Stankovich, Jim
AU  - Stankovich J
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 068545/Z/02/WT_/Wellcome Trust/United Kingdom
GR  - G0000934/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101026
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
SB  - IM
MH  - Alleles
MH  - Base Sequence
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Gene Dosage
MH  - *Genetic Predisposition to Disease
MH  - HLA-DP Antigens/*genetics
MH  - HLA-DP beta-Chains
MH  - Multiple Sclerosis/*genetics
MH  - *Polymorphism, Single Nucleotide
PMC - PMC2964313
COIS- Competing Interests: J.P.R. is currently employed by GlaxoSmithKline. This does 
      not alter the authors' adherence to all the PLoS ONE policies on sharing data and 
      materials.
EDAT- 2010/11/05 06:00
MHDA- 2011/03/08 06:00
PMCR- 2010/10/26
CRDT- 2010/11/05 06:00
PHST- 2010/06/20 00:00 [received]
PHST- 2010/08/26 00:00 [accepted]
PHST- 2010/11/05 06:00 [entrez]
PHST- 2010/11/05 06:00 [pubmed]
PHST- 2011/03/08 06:00 [medline]
PHST- 2010/10/26 00:00 [pmc-release]
AID - 10-PONE-RA-20012R1 [pii]
AID - 10.1371/journal.pone.0013454 [doi]
PST - epublish
SO  - PLoS One. 2010 Oct 26;5(10):e13454. doi: 10.1371/journal.pone.0013454.