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Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2; Strange, A; Capon, F; Spencer, CC; Knight, J; Weale, ME; Allen, MH; Barton, A; Band, G; Bellenguez, C; Bergboer, JG; Blackwell, JM; Bramon, E; Bumpstead, SJ; Casas, JP; Cork, MJ; Corvin, A; Deloukas, P; Dilthey, A; Duncanson, A; Edkins, S; Estivill, X; Fitzgerald, O; Freeman, C; Giardina, E; Gray, E; Hofer, A; Hüffmeier, U; Hunt, SE; Irvine, AD; Jankowski, J; Kirby, B; Langford, C; Lascorz, J; Leman, J; Leslie, S; Mallbris, L; Markus, HS; Mathew, CG; McLean, WH; McManus, R; Mössner, R; Moutsianas, L; Naluai, AT; Nestle, FO; Novelli, G; Onoufriadis, A; Palmer, CN; Perricone, C; Pirinen, M; Plomin, R; Potter, SC; Pujol, RM; Rautanen, A; Riveira-Munoz, E; Ryan, AW; Salmhofer, W; Samuelsson, L; Sawcer, SJ; Schalkwijk, J; Smith, CH; Ståhle, M; Su, Z; Tazi-Ahnini, R; Traupe, H; Viswanathan, AC; Warren, RB; Weger, W; Wolk, K; Wood, N; Worthington, J; Young, HS; Zeeuwen, PL; Hayday, A; Burden, AD; Griffiths, CE; Kere, J; Reis, A; McVean, G; Evans, DM; Brown, MA; Barker, JN; Peltonen, L; Donnelly, P; Trembath, RC.
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
Nat Genet. 2010; 42(11):985-990
Doi: 10.1038/ng.694
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
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Hofer Angelika
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Salmhofer Wolfgang
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Weger Wolfgang
- Study Group Members Med Uni Graz:
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Wolf Peter
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- Abstract:
- 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.
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Aminopeptidases - genetics
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Chromosome Mapping -
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Chromosomes, Human - genetics
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Chromosomes, Human, X - genetics
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Chromosomes, Human, X -
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Genetic Predisposition to Disease -
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Genetic Variation -
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Genome-Wide Association Study -
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HLA-C Antigens - genetics
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Humans -
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Major Histocompatibility Complex - genetics
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Polymorphism, Single Nucleotide -
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Psoriasis - genetics
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Reference Values -
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Risk Assessment -