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Am J Hum Genet DOI:10.1016/j.ajhg.2014.07.002

Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes.

Publication TypeJournal Article
Year of Publication2014
AuthorsOkada, Y, Han, B, Tsoi, LC, Stuart, PE, Ellinghaus, E, Tejasvi, T, Chandran, V, Pellett, F, Pollock, R, Bowcock, AM, Krueger, GG, Weichenthal, M, Voorhees, JJ, Rahman, P, Gregersen, PK, Franke, A, Nair, RP, Abecasis, GR, Gladman, DD, Elder, JT, de Bakker, PIW, Raychaudhuri, S
JournalAm J Hum Genet
Volume95
Issue2
Pages162-72
Date Published2014 Aug 07
ISSN1537-6605
KeywordsAmino Acid Sequence, Arthritis, Psoriatic, Base Sequence, Chromosome Mapping, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, HLA-B Antigens, HLA-C Antigens, Humans, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Psoriasis
Abstract

Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C(∗)06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10(-364)). Stepwise analysis revealed multiple HLA-C(∗)06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C(∗)12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0002-9297(14)00311-5
DOI10.1016/j.ajhg.2014.07.002
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25087609?dopt=Abstract

Alternate JournalAm. J. Hum. Genet.
PubMed ID25087609
PubMed Central IDPMC4129407
Grant ListR01 AR050266 / AR / NIAMS NIH HHS / United States
1R01AR062886 / AR / NIAMS NIH HHS / United States
R01 AR042742 / AR / NIAMS NIH HHS / United States
1R01AR063759-01A1 / AR / NIAMS NIH HHS / United States
R01AR062382 / AR / NIAMS NIH HHS / United States
U01 GM092691 / GM / NIGMS NIH HHS / United States
R01 AR050511 / AR / NIAMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
5U01GM092691-04 / GM / NIGMS NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
R01 AR062886 / AR / NIAMS NIH HHS / United States
R01 AR065183 / AR / NIAMS NIH HHS / United States
R01 AR063611 / AR / NIAMS NIH HHS / United States
2R01AR050266 / AR / NIAMS NIH HHS / United States
R01AR042742 / AR / NIAMS NIH HHS / United States
R01AR050511 / AR / NIAMS NIH HHS / United States