PMID- 19680446
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20221207
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 5
IP  - 8
DP  - 2009 Aug
TI  - Multiple Loci within the major histocompatibility complex confer risk of 
      psoriasis.
PG  - e1000606
LID - 10.1371/journal.pgen.1000606 [doi]
LID - e1000606
AB  - Psoriasis is a common inflammatory skin disease characterized by thickened scaly 
      red plaques. Previously we have performed a genome-wide association study (GWAS) 
      on psoriasis with 1,359 cases and 1,400 controls, which were genotyped for 
      447,249 SNPs. The most significant finding was for SNP rs12191877, which is in 
      tight linkage disequilibrium with HLA-Cw*0602, the consensus risk allele for 
      psoriasis. However, it is not known whether there are other psoriasis loci within 
      the MHC in addition to HLA-C. In the present study, we searched for additional 
      susceptibility loci within the human leukocyte antigen (HLA) region through 
      in-depth analyses of the GWAS data; then, we followed up our findings in an 
      independent Han Chinese 1,139 psoriasis cases and 1,132 controls. Using the 
      phased CEPH dataset as a reference, we imputed the HLA-Cw*0602 in all samples 
      with high accuracy. The association of the imputed HLA-Cw*0602 dosage with 
      disease was much stronger than that of the most significantly associated SNP, 
      rs12191877. Adjusting for HLA-Cw*0602, there were two remaining association 
      signals: one demonstrated by rs2073048 (p = 2 x 10(-6), OR = 0.66), located 
      within c6orf10, a potential downstream effecter of TNF-alpha, and one indicated 
      by rs13437088 (p = 9 x 10(-6), OR = 1.3), located 30 kb centromeric of HLA-B and 
      16 kb telomeric of MICA. When HLA-Cw*0602, rs2073048, and rs13437088 were all 
      included in a logistic regression model, each of them was significantly 
      associated with disease (p = 3 x 10(-47), 6 x 10(-8), and 3 x 10(-7), 
      respectively). Both putative loci were also significantly associated in the Han 
      Chinese samples after controlling for the imputed HLA-Cw*0602. A detailed 
      analysis of HLA-B in both populations demonstrated that HLA-B*57 was associated 
      with an increased risk of psoriasis and HLA-B*40 a decreased risk, independently 
      of HLA-Cw*0602 and the C6orf10 locus, suggesting the potential pathogenic 
      involvement of HLA-B. These results demonstrate that there are at least two 
      additional loci within the MHC conferring risk of psoriasis.
FAU - Feng, Bing-Jian
AU  - Feng BJ
AD  - Department of Dermatology, University of Utah School of Medicine, Salt Lake City, 
      UT, USA.
FAU - Sun, Liang-Dan
AU  - Sun LD
FAU - Soltani-Arabshahi, Razieh
AU  - Soltani-Arabshahi R
FAU - Bowcock, Anne M
AU  - Bowcock AM
FAU - Nair, Rajan P
AU  - Nair RP
FAU - Stuart, Philip
AU  - Stuart P
FAU - Elder, James T
AU  - Elder JT
FAU - Schrodi, Steven J
AU  - Schrodi SJ
FAU - Begovich, Ann B
AU  - Begovich AB
FAU - Abecasis, Goncalo R
AU  - Abecasis GR
FAU - Zhang, Xue-Jun
AU  - Zhang XJ
FAU - Callis-Duffin, Kristina P
AU  - Callis-Duffin KP
FAU - Krueger, Gerald G
AU  - Krueger GG
FAU - Goldgar, David E
AU  - Goldgar DE
LA  - eng
GR  - M01 RR000042/RR/NCRR NIH HHS/United States
GR  - R01 AR042742/AR/NIAMS NIH HHS/United States
GR  - R01 AR050511/AR/NIAMS NIH HHS/United States
GR  - M01 RR00042/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090814
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B40 Antigen)
RN  - 0 (HLA-B57 antigen)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*06:02 antigen)
SB  - IM
MH  - Adult
MH  - Asian People/ethnology/genetics
MH  - Case-Control Studies
MH  - Female
MH  - Genome-Wide Association Study
MH  - HLA-B Antigens/*genetics
MH  - HLA-B40 Antigen
MH  - HLA-C Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Psoriasis/ethnology/*genetics
MH  - Young Adult
PMC - PMC2718700
COIS- ABB and SJS own stock and/or stock options in Celera Corporation.
EDAT- 2009/08/15 09:00
MHDA- 2009/10/29 06:00
PMCR- 2009/08/01
CRDT- 2009/08/15 09:00
PHST- 2009/05/11 00:00 [received]
PHST- 2009/07/16 00:00 [accepted]
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
PHST- 2009/08/01 00:00 [pmc-release]
AID - 09-PLGE-RA-0779R2 [pii]
AID - 10.1371/journal.pgen.1000606 [doi]
PST - ppublish
SO  - PLoS Genet. 2009 Aug;5(8):e1000606. doi: 10.1371/journal.pgen.1000606. Epub 2009 
      Aug 14.