A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1

By A. Strange, F. Capon, Chris C. A. Spencer, J. Knight, M. Weale, M. Allen, A. Barton, G. Band, C. Bellenguez, Judith G. M. Bergboer and 74 more. Nature Genetics, 2010

1,032 citations recorded by the source corpus.

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10−8 and two loci with a combined P < 5 × 10−7). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10−6). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.

Subfields: Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/0092156faa99898086238b270d05efaeee88089a

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Citations in the corpus

• Major Histocompatibility Complex Genomics and Human Disease (2013, neutral): “Evidence has also been found for interaction involving HLA-C and a non-MHC gene, ERAP1, such that variants in ERAP1 exert an effect only in people with psoriasis who carry the HLA-C risk allele (112).”
• Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens (2013, background): “We and others have previously demonstrated the potential of HLA imputation for a wide range of phenotypes including host control of HIV-1 replication [17,26], rheumatoid arthritis [27], ulcerative colitis [28], primary biliary cirrhosis [29], psoriasis [30], ankylosing spondylitis [31], multiple scl”