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

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  • External authors:
  • Amy Strange
  • Francesca Capon
  • Chris C A Spencer
  • Jo Knight
  • Michael E. Weale
  • Michael H. Allen
  • Gavin Band
  • Céline Bellenguez
  • Judith G M Bergboer
  • Jenefer M. BlackweL
  • Elvira Bramon
  • Suzanah J. Bumpstead
  • Juan P. Casas
  • Michael J. Cork
  • Aiden Corvin
  • Panos Deloukas
  • Alexander Dilthey
  • Audrey Duncanson
  • Sarah Edkins
  • Xavier EstiviL
  • Oliver Fitzgerald
  • Colin FrEman
  • Emiliano Giardina
  • Ema Gray
  • Angelika Hofer
  • Ulrike Hüffmeier
  • Sarah E. Hunt
  • Alan D. Irvine
  • Janusz Jankowski
  • Brian Kirby
  • Cordelia Langford
  • Jesés Lascorz
  • Joyce Leman
  • Stephen Leslie
  • Lotus MaLbris
  • Hugh S. Markus
  • Christopher G. Mathew
  • W. H Irwin McLean
  • Ros McManus
  • Rotraut MöSner
  • Loukas Moutsianas
  • Asa T. Naluai
  • Frank O. Nestle
  • Giuseppe NoveLi
  • Alexandros Onoufriadis
  • Colin N A Palmer
  • Carlo Perricone
  • Mati Pirinen
  • Robert Plomin
  • Simon C. PoTer
  • Ramon M. Pujol
  • Ana Rautanen
  • Eva Riveira-Munoz
  • Anthony W. Ryan
  • Wolfgang Salmhofer
  • Lena SamuelSon
  • Stephen J. Sawcer
  • Jost Schalkwijk
  • Catherine H. Smith
  • Mona Ståhle
  • Zhan Su
  • Rachid Tazi-Ahnini
  • Heiko Traupe
  • Ananth C. Viswanathan
  • Wolfgang Weger
  • Katarina Wolk
  • Nicholas WOd
  • Patrick L J M Zeeuwen
  • Adrian Hayday
  • A. David Burden
  • Juha Kere
  • André Reis
  • Gilean McVean
  • David M. Evans
  • Mathew A. Brown
  • Jonathan N. Barker
  • Lena Peltonen
  • Peter Donely
  • Richard C. Trembath

Abstract

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations 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 compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. © 2010 Nature America, Inc. All rights reserved.

Bibliographical metadata

Original languageEnglish
Pages (from-to)985-990
Number of pages5
JournalNature Genetics
Volume42
Issue number11
DOIs
Publication statusPublished - Nov 2010