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

Amy Strange; Francesca Capon; Chris C. A. Spencer; Jo Knight; Michael E. Weale; Michael H. Allen; Anne Barton; Gavin Band; Celine Bellenguez; Judith G. M. Bergboer; Jenefer M. Blackwell; Elvira Bramon; Suzannah J. Bumpstead; Juan P. Casas; Michael J. Cork; Aiden Corvin; Panos Deloukas; Alexander Dilthey; Audrey Duncanson; Sarah Edkins; Xavier Estivill; Oliver Fitzgerald; Colin Freeman; Emiliano Giardina; Emma Gray; Angelika Hofer; Ulrike Hueffmeier; Sarah E. Hunt; Alan D. Irvine; Janusz Jankowski; Brian Kirby; Cordelia Langford; Jesus Lascorz; Joyce Leman; Stephen Leslie; Lotus Mallbris; Hugh S. Markus; Christopher G. Mathew; W. H. Irwin McLean; Ross McManus; Rotraut Moessner; Loukas Moutsianas; Asa T. Naluai; Frank O. Nestle; Giuseppe Novelli; Alexandros Onoufriadis; Colin N. A. Palmer; Carlo Perricone; Matti Pirinen; Robert Plomin; Simon C. Potter; Ramon M. Pujol; Anna Rautanen; Eva Riveira-Munoz; Anthony W. Ryan; Wolfgang Salmhofer; Lena Samuelsson; Stephen J. Sawcer; Joost Schalkwijk; Catherine H. Smith; Mona Stahle; Zhan Su; Rachid Tazi-Ahnini; Heiko Traupe; Ananth C. Viswanathan; Richard B. Warren; Wolfgang Weger; Katarina Wolk; Nicholas Wood; Jane Worthington; Helen S. Young; Patrick L. J. M. Zeeuwen; Adrian Hayday; A. David Burden; Christopher E. M. Griffiths; Juha Kere; Andre Reis; Gilean McVean; David M. Evans; Matthew A. Brown; Jonathan N. Barker; Leena Peltonen; Peter Donnelly; Richard C. Trembath; Wellcome Trust Case Control

doi:10.1038/ng.694

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

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

Amy Strange, Francesca Capon, Chris C. A. Spencer, Jo Knight, Michael E. Weale, Michael H. Allen, Anne Barton, Gavin Band, Celine Bellenguez, Judith G. M. Bergboer, …

Nature genetics, Vol.42(11), pp.985-U106

01/11/2010

DOI: https://doi.org/10.1038/ng.694

PMCID: PMC3749730

PMID: 20953190

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 10(-8) and two loci with a combined P < 5 x 10(-7)). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 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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Title: A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
Creators - without role: Amy Strange - University of Oxford
Francesca Capon - King's College London
Chris C. A. Spencer - University of Oxford
Jo Knight - College Station Medical Center
Michael E. Weale - King's College London
Michael H. Allen - College Station Medical Center
Anne Barton - University of Manchester
Gavin Band - University of Oxford
Celine Bellenguez - University of Oxford
Judith G. M. Bergboer - Radboud University Nijmegen
Jenefer M. Blackwell - College Station Medical Center
Elvira Bramon - College Station Medical Center
Suzannah J. Bumpstead - Wellcome Sanger Institute
Juan P. Casas - University of London
Michael J. Cork - University of Sheffield
Aiden Corvin - Trinity College Dublin
Panos Deloukas - Wellcome Sanger Institute
Alexander Dilthey - University of Oxford
Audrey Duncanson - Wellcome Trust
Sarah Edkins - Wellcome Sanger Institute
Xavier Estivill - CRG, Genes & Dis Programme, Barcelona, Spain
Oliver Fitzgerald - St Vincents Univ Hosp, Dublin 4, Ireland
Colin Freeman - Wellcome Trust
Emiliano Giardina - Supreme Council Of Health
Emma Gray - Wellcome Sanger Institute
Angelika Hofer - Medical University of Graz
Ulrike Hueffmeier - Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany
Sarah E. Hunt - Wellcome Sanger Institute
Alan D. Irvine - Trinity College Dublin
Janusz Jankowski - Queen Mary University of London
Brian Kirby - St Vincents Univ Hosp, Dublin 4, Ireland
Cordelia Langford - Wellcome Sanger Institute
Jesus Lascorz - Heidelberg
Joyce Leman - Western Infirmary
Stephen Leslie - University of Oxford
Lotus Mallbris - Karolinska Institutet
Hugh S. Markus - St George's, University of London
Christopher G. Mathew - King's College London
W. H. Irwin McLean - University of Dundee
Ross McManus - Trinity College Dublin
Rotraut Moessner - University of Göttingen
Loukas Moutsianas - University of Oxford
Asa T. Naluai - University of Gothenburg
Frank O. Nestle - College Station Medical Center
Giuseppe Novelli - Supreme Council Of Health
Alexandros Onoufriadis - King's College London
Colin N. A. Palmer - University of Dundee
Carlo Perricone - Sapienza University of Rome
Matti Pirinen - University of Oxford
Robert Plomin - King's College London
Simon C. Potter - Wellcome Sanger Institute
Ramon M. Pujol - Hosp del Mar, IMAS, Dermatol Serv, Barcelona, Spain
Anna Rautanen - Wellcome Trust
Eva Riveira-Munoz - CRG, Genes & Dis Programme, Barcelona, Spain
Anthony W. Ryan - College Station Medical Center
Wolfgang Salmhofer - Medical University of Graz
Lena Samuelsson - University of Gothenburg
Stephen J. Sawcer - University of Cambridge
Joost Schalkwijk - Radboud University Nijmegen
Catherine H. Smith - College Station Medical Center
Mona Stahle - Karolinska Institutet
Zhan Su - Wellcome Trust
Rachid Tazi-Ahnini - University of Sheffield
Heiko Traupe - University of Münster
Ananth C. Viswanathan - University College London
Richard B. Warren - University of Manchester
Wolfgang Weger - Medical University of Graz
Katarina Wolk - Karolinska Institutet
Nicholas Wood - Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Jane Worthington - University of Manchester
Helen S. Young - University of Manchester
Patrick L. J. M. Zeeuwen - Radboud University Nijmegen
Adrian Hayday - University of Cambridge
A. David Burden - Western Infirm & Associated Hosp, Dept Dermatol, Glasgow, Lanark, Scotland
Christopher E. M. Griffiths - University of Manchester
Juha Kere - Karolinska Institutet
Andre Reis - Friedrich-Alexander-Universität Erlangen-Nürnberg
Gilean McVean - University of Oxford
David M. Evans - University of Bristol
Matthew A. Brown - University of Queensland
Jonathan N. Barker - College Station Medical Center
Leena Peltonen - Wellcome Sanger Institute
Peter Donnelly - University of Oxford
Richard C. Trembath - College Station Medical Center
Wellcome Trust Case Control
Publication Details: Nature genetics, Vol.42(11), pp.985-U106
Publisher: Springer Nature
Number of pages: 8
Grant note: 083948/Z/07/Z / Wellcome Trust Department of Health through the National Institute for Health Research (NIHR); National Institutes of Health Research (NIHR) Psoriasis Association and the Cecil King Memorial Foundation Genetic Repository in Ireland for Psoriasis and Psoriatic Arthritis Karolinska University Hospital; Karolinska Institutet Generation Trust St. Thomas' National Health Service (NHS) Foundation Trust Departments of Health and Universities and Innovation 17552 / Arthritis Research UK; Versus Arthritis G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 078173/Z/05/Z; 068545/Z/02 / Wellcome Trust and Science Foundation Ireland; Science Foundation Ireland G0901310; G19/2; G0000934; G0600705; G0800582; G0601387; G0700314 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Tr 228/5-4; Re 679/104 / German Research Foundation; German Research Foundation (DFG) AFA Insurance and Welander Finsen Foundation National Institute for Health Research; National Institutes of Health Research (NIHR) Karolinska Institutet Netherlands Organization for Health Research and Development (P.L.J.M.Z.); Netherlands Organization for Health Research and Development Wolfson-Royal Society; Royal Society Psoriasis Foundation Irish Health Research Board; Health Research Board - Ireland SAF 2008-00357 / Spanish Ministry of Science and Innovation; Spanish Government Association for the Defence of Psoriasis Patients Manchester Biomedical Research Centre; National Institutes of Health Research (NIHR) IZKF B32/A8 / Interdisciplinary Centre for Clinical Research of the University of Erlangen-Nuremberg Swedish Medical Research Council; Swedish Medical Research Council (SMRC) G0000934; G0600698B; G0600705; G0700314; G9817803B; G19/2; G0601387; G0901310; G0800582 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0601387 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) King's College London; General Electric CL-2008-06-002; PDA/02/06/016; NF-SI-0507-10379 / National Institute for Health Research; National Institutes of Health Research (NIHR) Swedish Psoriasis Association
Identifiers: 9936062208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article