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Publication Detail
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    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, Huffmeier 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, Mossner 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, Stahle 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
  • Publication date:
    2010
  • Pagination:
    985, 990
  • Volume:
    42
  • Medium:
    11
  • Print ISSN:
    1546-1718
  • Keywords:
    Aminopeptidases/*genetics Chromosome Mapping Chromosomes, Human/genetics Chromosomes, Human, X/genetics Europe *Genetic Predisposition to Disease Genetic Variation *Genome-Wide Association Study HLA-C Antigens/*genetics Humans Major Histocompatibility Complex/genetics Polymorphism, Single Nucleotide Psoriasis/*genetics Reference Values Risk Assessment
  • Notes:
    Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2 Strange, Amy Capon, Francesca Spencer, Chris C A Knight, Jo Weale, Michael E Allen, Michael H Barton, Anne Band, Gavin Bellenguez, Celine Bergboer, Judith G M Blackwell, Jenefer M Bramon, Elvira Bumpstead, Suzannah J Casas, Juan P Cork, Michael J Corvin, Aiden Deloukas, Panos Dilthey, Alexander Duncanson, Audrey Edkins, Sarah Estivill, Xavier Fitzgerald, Oliver Freeman, Colin Giardina, Emiliano Gray, Emma Hofer, Angelika Huffmeier, Ulrike Hunt, Sarah E Irvine, Alan D Jankowski, Janusz Kirby, Brian Langford, Cordelia Lascorz, Jesus Leman, Joyce Leslie, Stephen Mallbris, Lotus Markus, Hugh S Mathew, Christopher G McLean, W H Irwin McManus, Ross Mossner, Rotraut Moutsianas, Loukas Naluai, Asa T Nestle, Frank O Novelli, Giuseppe Onoufriadis, Alexandros Palmer, Colin N A Perricone, Carlo Pirinen, Matti Plomin, Robert Potter, Simon C Pujol, Ramon M Rautanen, Anna Riveira-Munoz, Eva Ryan, Anthony W Salmhofer, Wolfgang Samuelsson, Lena Sawcer, Stephen J Schalkwijk, Joost Smith, Catherine H Stahle, Mona Su, Zhan Tazi-Ahnini, Rachid Traupe, Heiko Viswanathan, Ananth C Warren, Richard B Weger, Wolfgang Wolk, Katarina Wood, Nicholas Worthington, Jane Young, Helen S Zeeuwen, Patrick L J M Hayday, Adrian Burden, A David Griffiths, Christopher E M Kere, Juha Reis, Andre McVean, Gilean Evans, David M Brown, Matthew A Barker, Jonathan N Peltonen, Leena Donnelly, Peter Trembath, Richard C 068545/Z/02/Wellcome Trust/United Kingdom 083948/Z/07/Z/Wellcome Trust/United Kingdom G0000934/Medical Research Council/United Kingdom G0601387/Medical Research Council/United Kingdom Department of Health/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Nature genetics Nat Genet. 2010 Nov;42(11):985-90. Epub 2010 Oct 17. 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 and two loci with a combined P < 5 x 10). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 10). 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.
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 x 10 and two loci with a combined P < 5 x 10). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 10). 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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