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

被引：812

作者：

Strange, Amy ^{[1
]}

Capon, Francesca ^{[2
]}

Spencer, Chris C. A. ^{[1
]}

Knight, Jo ^{[2
,3
]}

Weale, Michael E. ^{[2
]}

Allen, Michael H. ^{[2
]}

Barton, Anne ^{[4
]}

Band, Gavin ^{[1
]}

Bellenguez, Celine ^{[1
]}

Bergboer, Judith G. M. ^{[5
]}

Blackwell, Jenefer M. ^{[6
]}

Bramon, Elvira ^{[7
,8
]}

Bumpstead, Suzannah J. ^{[9
]}

Casas, Juan P. ^{[10
]}

Cork, Michael J. ^{[11
]}

Corvin, Aiden ^{[12
]}

Deloukas, Panos ^{[9
]}

Dilthey, Alexander ^{[13
]}

Duncanson, Audrey ^{[14
]}

Edkins, Sarah ^{[9
]}

Estivill, Xavier ^{[15
,16
]}

Fitzgerald, Oliver ^{[17
]}

Freeman, Colin ^{[1
]}

Giardina, Emiliano ^{[18
]}

Gray, Emma ^{[9
]}

Hofer, Angelika ^{[19
]}

Hueffmeier, Ulrike ^{[20
]}

Hunt, Sarah E. ^{[9
]}

Irvine, Alan D. ^{[21
]}

Jankowski, Janusz ^{[22
]}

Kirby, Brian ^{[17
]}

Langford, Cordelia ^{[9
]}

Lascorz, Jesus ^{[23
]}

Leman, Joyce ^{[24
]}

Leslie, Stephen ^{[13
]}

Mallbris, Lotus ^{[25
]}

Markus, Hugh S. ^{[26
]}

Mathew, Christopher G. ^{[2
]}

McLean, W. H. Irwin ^{[27
,28
,29
]}

McManus, Ross ^{[30
,31
]}

Moessner, Rotraut ^{[32
]}

Moutsianas, Loukas ^{[13
]}

Naluai, Asa T. ^{[33
]}

Nestle, Frank O. ^{[2
,3
]}

Novelli, Giuseppe ^{[18
]}

Onoufriadis, Alexandros ^{[2
]}

Palmer, Colin N. A. ^{[34
]}

Perricone, Carlo ^{[35
]}

Pirinen, Matti ^{[1
]}

Plomin, Robert ^{[36
]}

机构：

[1] Wellcome Trust Ctr Human Genet, Oxford, England

[2] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England

[3] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Biomed Res Ctr, NIHR, London, England

[4] Univ Manchester, UK Epidemiol Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[5] Radboud Univ Nijmegen Med Ctr, Dept Dermatol, Nijmegen, Netherlands

[6] Addenbrookes Hosp, Cambridge Inst Med Res, Genet & Infect Lab, Cambridge, England

[7] Kings Coll London, Div Psychol Med & Psychiat, Biomed Res Ctr Mental Hlth, Inst Psychiat, London WC2R 2LS, England

[8] S London & Maudsley NHS Fdn Trust, London, England

[9] Wellcome Trust Sanger Inst, Cambridge, England

[10] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England

[11] Univ Sheffield, Dept Infect & Immun, Acad Unit Dermatol Res, Sheffield, S Yorkshire, England

[12] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland

[13] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[14] Wellcome Trust Res Labs, London, England

[15] CRG, Genes & Dis Programme, Barcelona, Spain

[16] Publ Hlth & Epidemiol Network Biomed Res Ctr CIBE, Barcelona, Spain

[17] St Vincents Univ Hosp, Dublin 4, Ireland

[18] Univ Roma Tor Vergata, Sch Med, Dept Biopathol, Ctr Excellence Genom Risk Assessment Multifactori, Rome, Italy

[19] Med Univ Graz, Dept Dermatol, Graz, Austria

[20] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany

[21] Our Ladys Childrens Hosp Crumlin, Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland

[22] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London, England

[23] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany

[24] Western Infirm & Associated Hosp, Dept Dermatol, Glasgow, Lanark, Scotland

[25] Karolinska Inst, Dept Med, Dermatol Unit, Stockholm, Sweden

[26] St Georges Univ London, London, England

[27] Univ Dundee, Div Mol Med, Epithelial Genet Grp, Coll Life Sci & Med, Dundee, Scotland

[28] Univ Dundee, Div Mol Med, Epithelial Genet Grp, Coll Dent, Dundee, Scotland

[29] Univ Dundee, Div Mol Med, Epithelial Genet Grp, Coll Nursing, Dundee, Scotland

[30] St James Hosp, Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland

[31] St James Hosp, Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland

[32] Univ Gottingen, Dept Dermatol, Gottingen, Germany

[33] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med & Clin Genet, Gothenburg, Sweden

[34] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland

[35] Univ Roma La Sapienza, Rheumatol Unit, Dept Clin & Med Therapy, Rome, Italy

[36] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England

[37] Hosp del Mar, IMAS, Dermatol Serv, Barcelona, Spain

[38] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England

[39] Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England

[40] Univ Munster, Dept Dermatol, D-4400 Munster, Germany

[41] Moorfields Eye Hosp NHS Fdn Trust, Glaucoma Res Unit, London, England

[42] UCL, Dept Genet, Inst Ophthalmol, London, England

[43] Univ Manchester, Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[44] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[45] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England

[46] London Res Inst, Immuno Surveillance Lab, London, England

[47] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden

[48] Sci Life Lab, Stockholm, Sweden

[49] Folkhalsan Inst Genet, Helsinki, Finland

[50] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

STATISTICAL-METHOD; DISEASES; GENE; VARIANTS; AUTOIMMUNITY; RESPONSES; PATHWAYS; COMPLEX; FAMILY; SCAN;

D O I：

10.1038/ng.694

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：985 / U106

页数：8

共 50 条

[21] Genome-wide association study identifies five new breast cancer susceptibility loci
Clare Turnbull
Shahana Ahmed
Jonathan Morrison
David Pernet
Anthony Renwick
Mel Maranian
Sheila Seal
Maya Ghoussaini
Sarah Hines
Catherine S Healey
Deborah Hughes
Margaret Warren-Perry
William Tapper
Diana Eccles
D Gareth Evans
Maartje Hooning
Mieke Schutte
Ans van den Ouweland
Richard Houlston
Gillian Ross
Cordelia Langford
Paul D P Pharoah
Michael R Stratton
Alison M Dunning
Nazneen Rahman
Douglas F Easton
Nature Genetics, 2010, 42 : 504 - 507
[22] Genome-wide association study identifies five susceptibility loci for glioma
Sanjay Shete
Fay J Hosking
Lindsay B Robertson
Sara E Dobbins
Marc Sanson
Beatrice Malmer
Matthias Simon
Yannick Marie
Blandine Boisselier
Jean-Yves Delattre
Khe Hoang-Xuan
Soufiane El Hallani
Ahmed Idbaih
Diana Zelenika
Ulrika Andersson
Roger Henriksson
A Tommy Bergenheim
Maria Feychting
Stefan Lönn
Anders Ahlbom
Johannes Schramm
Michael Linnebank
Kari Hemminki
Rajiv Kumar
Sarah J Hepworth
Amy Price
Georgina Armstrong
Yanhong Liu
Xiangjun Gu
Robert Yu
Ching Lau
Minouk Schoemaker
Kenneth Muir
Anthony Swerdlow
Mark Lathrop
Melissa Bondy
Richard S Houlston
Nature Genetics, 2009, 41 : 899 - 904
[23] Genome-wide association study identifies two susceptibility loci for osteosarcoma
Savage, Sharon A.
Mirabello, Lisa
Wang, Zhaoming
Gastier-Foster, Julie M.
Gorlick, Richard
Khanna, Chand
Flanagan, Adrienne M.
Tirabosco, Roberto
Andrulis, Irene L.
Wunder, Jay S.
Gokgoz, Nalan
Patino-Garcia, Ana
Sierrasesumaga, Luis
Lecanda, Fernando
Kurucu, Nilgun
Ilhan, Inci Ergurhan
Sari, Neriman
Serra, Massimo
Hattinger, Claudia
Picci, Piero
Spector, Logan G.
Barkauskas, Donald A.
Marina, Neyssa
Caminada de Toledo, Silvia Regina
Petrilli, Antonio S.
Amary, Maria Fernanda
Halai, Dina
Thomas, David M.
Douglass, Chester
Meltzer, Paul S.
Jacobs, Kevin
Chung, Charles C.
Berndt, Sonja I.
Purdue, Mark P.
Caporaso, Neil E.
Tucker, Margaret
Rothman, Nathaniel
Landi, Maria Teresa
Silverman, Debra T.
Kraft, Peter
Hunter, David J.
Malats, Nuria
Kogevinas, Manolis
Wacholder, Sholom
Troisi, Rebecca
Helman, Lee
Fraumeni, Joseph F., Jr.
Yeager, Meredith
Hoover, Robert N.
Chanock, Stephen J.
NATURE GENETICS, 2013, 45 (07) : 799 - 803
[24] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
Kunz, Manfred
Koenig, Inke R.
Schillert, Arne
Kruppa, Jochen
Ziegler, Andreas
Grallert, Harald
Mueller-Nurasyid, Martina
Lieb, Wolfgang
Franke, Andre
Ranki, Annamari
Panelius, Jaana
Koskenmies, Sari
Hasan, Taina
Kere, Juha
Roenn, Ann-Charlotte
Simon, Jan C.
Schmidt, Enno
Wenzel, Joerg
Tueting, Thomas
Landsberg, Jennifer
Zeller, Tanja
Blankenberg, Stefan
Glaeser, Regine
Patsinakidis, Nikolaos
Kuhn, Annegret
Ibrahim, Saleh M.
EXPERIMENTAL DERMATOLOGY, 2015, 24 (07) : 510 - 515
[25] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
Jin-Xin Bei
Yi Li
Wei-Hua Jia
Bing-Jian Feng
Gangqiao Zhou
Li-Zhen Chen
Qi-Sheng Feng
Hui-Qi Low
Hongxing Zhang
Fuchu He
E Shyong Tai
Tiebang Kang
Edison T Liu
Jianjun Liu
Yi-Xin Zeng
Nature Genetics, 2010, 42 : 599 - 603
[26] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
Kunz, M.
Koenig, I. R.
Ziegler, A.
Ranki, A.
Koskenmies, S.
Ronn, A.
Simon, J. C.
Wenzel, J.
Landsberg, J.
Zeller, T.
Glaeser, R.
Kuhn, A.
Ibrahim, S.
EXPERIMENTAL DERMATOLOGY, 2016, 25 (03) : E18 - E18
[27] Genome-wide association study identifies susceptibility loci for IgA nephropathy
Ali G Gharavi
Krzysztof Kiryluk
Murim Choi
Yifu Li
Ping Hou
Jingyuan Xie
Simone Sanna-Cherchi
Clara J Men
Bruce A Julian
Robert J Wyatt
Jan Novak
John C He
Haiyan Wang
Jicheng Lv
Li Zhu
Weiming Wang
Zhaohui Wang
Kasuhito Yasuno
Murat Gunel
Shrikant Mane
Sheila Umlauf
Irina Tikhonova
Isabel Beerman
Silvana Savoldi
Riccardo Magistroni
Gian Marco Ghiggeri
Monica Bodria
Francesca Lugani
Pietro Ravani
Claudio Ponticelli
Landino Allegri
Giuliano Boscutti
Giovanni Frasca
Alessandro Amore
Licia Peruzzi
Rosanna Coppo
Claudia Izzi
Battista Fabio Viola
Elisabetta Prati
Maurizio Salvadori
Renzo Mignani
Loreto Gesualdo
Francesca Bertinetto
Paola Mesiano
Antonio Amoroso
Francesco Scolari
Nan Chen
Hong Zhang
Richard P Lifton
Nature Genetics, 2011, 43 : 321 - 327
[28] A genome-wide association study identifies susceptibility loci for Wilms tumor
Clare Turnbull
Elizabeth R Perdeaux
David Pernet
Arlene Naranjo
Anthony Renwick
Sheila Seal
Rosa Maria Munoz-Xicola
Sandra Hanks
Ingrid Slade
Anna Zachariou
Margaret Warren-Perry
Elise Ruark
Mary Gerrard
Juliet Hale
Martin Hewitt
Janice Kohler
Sheila Lane
Gill Levitt
Mabrook Madi
Bruce Morland
Veronica Neefjes
James Nicholson
Susan Picton
Barry Pizer
Milind Ronghe
Michael Stevens
Heidi Traunecker
Charles A Stiller
Kathy Pritchard-Jones
Jeffrey Dome
Paul Grundy
Nazneen Rahman
Nature Genetics, 2012, 44 : 681 - 684
[29] Genome-wide association study identifies five susceptibility loci for glioma
Shete, Sanjay
Hosking, Fay J.
Robertson, Lindsay B.
Dobbins, Sara E.
Sanson, Marc
Malmer, Beatrice
Simon, Matthias
Marie, Yannick
Boisselier, Blandine
Delattre, Jean-Yves
Hoang-Xuan, Khe
El Hallani, Soufiane
Idbaih, Ahmed
Zelenika, Diana
Andersson, Ulrika
Henriksson, Roger
Bergenheim, A. Tommy
Feychting, Maria
Lonn, Stefan
Ahlbom, Anders
Schramm, Johannes
Linnebank, Michael
Hemminki, Kari
Kumar, Rajiv
Hepworth, Sarah J.
Price, Amy
Armstrong, Georgina
Liu, Yanhong
Gu, Xiangjun
Yu, Robert
Lau, Ching
Schoemaker, Minouk
Muir, Kenneth
Swerdlow, Anthony
Lathrop, Mark
Bondy, Melissa
Houlston, Richard S.
NATURE GENETICS, 2009, 41 (08) : 899 - U54
[30] A genome-wide association study identifies susceptibility loci for Wilms tumor
Turnbull, Clare
Perdeaux, Elizabeth R.
Pernet, David
Naranjo, Arlene
Renwick, Anthony
Seal, Sheila
Munoz-Xicola, Rosa Maria
Hanks, Sandra
Slade, Ingrid
Zachariou, Anna
Warren-Perry, Margaret
Ruark, Elise
Gerrard, Mary
Hale, Juliet
Hewitt, Martin
Kohler, Janice
Lane, Sheila
Levitt, Gill
Madi, Mabrook
Morland, Bruce
Neefjes, Veronica
Nicholdson, James
Picton, Susan
Pizer, Barry
Ronghe, Milind
Stevens, Michael
Traunecker, Heidi
Stiller, Charles A.
Pritchard-Jones, Kathy
Dome, Jeffrey
Grundy, Paul
Rahman, Nazneen
NATURE GENETICS, 2012, 44 (06) : 681 - U100

← 1 2 3 4 5 →