Journal Article

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

Rautanen, Anna, Bramon, Elvira, Leman, Joyce, Riveira-Munoz, Eva, Naluai, Asa T, Plomin, Robert, Jankowski, Janusz, Worthington, Jane, Lascorz, Jesús, Pirinen, Matti, Barton, Anne, Ståhle, Mona, Trembath, Richard C, Giardina, Emiliano, Young, Helen S, Estivill, Xavier, Salmhofer, Wolfgang, Band, Gavin, Markus, Hugh S, Hunt, Sarah E, Irvine, Alan D, Palmer, Colin N A, Kere, Juha, Wolk, Katarina, Deloukas, Panos, McManus, Ross, Donnelly, Peter, Novelli, Giuseppe, Mathew, Christopher G, Sawcer, Stephen J, Hüffmeier, Ulrike, Hofer, Angelika, Edkins, Sarah, Tazi-Ahnini, Rachid, Kirby, Brian, Reis, André, Fitzgerald, Oliver, Barker, Jonathan N, Peltonen, Leena, Duncanson, Audrey, McLean, W H Irwin, Onoufriadis, Alexandros, Cork, Michael J, Evans, David M, Warren, Richard B, Dilthey, Alexander, Nestle, Frank O, Viswanathan, Ananth C, Weger, Wolfgang, Strange, Amy, Su, Zhan, Potter, Simon C, Pujol, Ramon M, Langford, Cordelia, Freeman, Colin, Moutsianas, Loukas, Ryan, Anthony W, Traupe, Heiko, Capon, Francesca, Zeeuwen, Patrick L J M, Blackwell, Jenefer M, Mössner, Rotraut, Knight, Jo, Leslie, Stephen, Griffiths, Chris

2010

Overview

Richard Trembath, Peter Donnelly and colleagues report a genome-wide association study identifying six new psoriasis susceptibility loci. They also identify a statistical interaction between HLA-C and ERAP1 in psoriasis susceptibility. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/205/2138 / 631/208/2490 / 631/250/249/2510/1758 / Agriculture / Aminopeptidases - genetics / Animal Genetics and Genomics / autoimmunity / Biological and medical sciences / Biomedical and Life Sciences / Biomedical research / Biomedicine / Cancer Research / Care and treatment / Chromosome Mapping / Chromosomes, Human - genetics / Chromosomes, Human, X - genetics / complex / Deoxyribonucleic acid / Dermatology / Disease susceptibility / diseases / DNA / Europe / family / Fundamental and applied biological sciences. Psychology / gene / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetic Variation / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Health aspects / Health services / Histocompatibility antigens / HLA histocompatibility antigens / HLA-C Antigens - genetics / Human Genetics / Humans / letter / Major Histocompatibility Complex - genetics / Medical Genetics and Genomics / Medical research / Medical sciences / Medicinsk genetik och genomik / Minor Histocompatibility Antigens / pathways / Polymorphism, Single Nucleotide / Principal components analysis / Psoriasis / Psoriasis - genetics / Psoriasis. Parapsoriasis. Lichen / Quality control / Reference Values / responses / Risk Assessment / scan / Skin diseases / statistical-method / variants