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.

Strange, A., Capon, F., Spencer, C., Knight, J., Weale, M., Allen, M., et al. (2010). A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. NATURE GENETICS, 42(11), 985-990 [10.1038/ng.694].

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

GIARDINA, EMILIANO;NOVELLI, GIUSEPPE;
2010-11-01

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.
nov-2010
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/03 - GENETICA MEDICA
English
Con Impact Factor ISI
Risk Assessment; Chromosome Mapping; Chromosomes, Human; Genetic Variation; Polymorphism, Single Nucleotide; Aminopeptidases; HLA-C Antigens; Humans; Major Histocompatibility Complex; Psoriasis; Europe; Genome-Wide Association Study; Reference Values; Genetic Predisposition to Disease; Chromosomes, Human, X
Strange, A., Capon, F., Spencer, C., Knight, J., Weale, M., Allen, M., et al. (2010). A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. NATURE GENETICS, 42(11), 985-990 [10.1038/ng.694].
Strange, A; Capon, F; Spencer, C; Knight, J; Weale, M; Allen, M; Barton, A; Band, G; Bellenguez, C; Bergboer, J; Blackwell, J; Bramon, E; Bumpstead, S; Casas, J; Cork, M; 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, S; Irvine, A; Jankowski, J; Kirby, B; Langford, C; Lascorz, J; Leman, J; Leslie, S; Mallbris, L; Markus, H; Mathew, C; Mclean, W; Mcmanus, R; Mössner, R; Moutsianas, L; Naluai, A; Nestle, F; Novelli, G; Onoufriadis, A; Palmer, C; Perricone, C; Pirinen, M; Plomin, R; Potter, S; Pujol, R; Rautanen, A; Riveira Munoz, E; Ryan, A; Salmhofer, W; Samuelsson, L; Sawcer, S; Schalkwijk, J; Smith, C; Ståhle, M; Su, Z; Tazi Ahnini, R; Traupe, H; Viswanathan, A; Warren, R; Weger, W; Wolk, K; Wood, N; Worthington, J; Young, H; Zeeuwen, P; Hayday, A; Burden, A; Griffiths, C; Kere, J; Reis, A; Mcvean, G; Evans, D; Brown, M; Barker, J; Peltonen, L; Donnelly, P; Trembath, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/10343
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