Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis

Knight, Jo, Spain, Sarah L., Capon, Francesca, Hayday, Adrian, Nestle, Frank O., Clop, Alex, Wellcome Trust Case Control Consortium, Brown, Matthew A., Genetic Analysis of Psoriasis Consortium, Barker, Jonathan N., Weale, Michael E. and Trembath, Richard C. (2012) Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis. Human Molecular Genetics, 21 23: 5185-5192. doi:10.1093/hmg/dds344


Author Knight, Jo
Spain, Sarah L.
Capon, Francesca
Hayday, Adrian
Nestle, Frank O.
Clop, Alex
Wellcome Trust Case Control Consortium
Brown, Matthew A.
Genetic Analysis of Psoriasis Consortium
Barker, Jonathan N.
Weale, Michael E.
Trembath, Richard C.
Total Author Count Override 143
Title Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1093/hmg/dds344
Volume 21
Issue 23
Start page 5185
End page 5192
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted abstract
Psoriasis is a common, chronic, inflammatory skin disorder. A number of genetic loci have been shown to confer risk for psoriasis. Collectively, these offer an integrated model for the inherited basis for susceptibility to psoriasis that combines altered skin barrier function together with the dysregulation of innate immune pathogen sensing and adap­tive immunity. The major histocompatibility complex (MHC) harbours the psoriasis susceptibility region which exhibits the largest effect size, driven in part by variation contained on the HLA-Cw*0602 allele. However, the resolution of the number and genomic location of potential independent risk loci are hampered by extensive linkage disequilibrium across the region. We leveraged the power of large psoriasis case and control data sets and the statistical approach of conditional analysis to identify potential further association signals distributed across the MHC. In addition to the major loci at HLA-C (P = 2.20 × 10−236), we observed and replicated four additional independent signals for disease association, three of which are novel. We detected evidence for association at SNPs rs2507971 (P = 6.73 × 10−14), rs9260313 (P = 7.93 × 10−09), rs66609536 (P = 3.54 × 10−07) and rs380924 (P = 6.24 × 10−06), located within the class I region of the MHC, with each observation replicated in an independent sample (P ≤ 0.01). The previously identified locus is close to MICA, the other three lie near MICB, HLA-A and HCG9 (a non-coding RNA gene). The identification of disease associations with both MICA and MICB is particularly intriguing, since each encodes an MHC class I-related protein with potent immunological function.
Keyword Genome-wide association
Classical HLA alleles
Susceptibility loci
Rheumatoid-arthritis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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Created: Mon, 15 Apr 2013, 11:29:12 EST by Kylie Hengst on behalf of UQ Diamantina Institute