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

[41] Genotypic variability-based genome-wide association study identifies non-additive loci HLA-C and IL12B for psoriasis
Wei, Wen-Hua
Massey, Jonathan
Worthington, Jane
Barton, Anne
Warren, Richard B.
JOURNAL OF HUMAN GENETICS, 2018, 63 (03) : 289 - 296
[42] Genotypic variability-based genome-wide association study identifies non-additive loci HLA-C and IL12B for psoriasis
Wen-Hua Wei
Jonathan Massey
Jane Worthington
Anne Barton
Richard B. Warren
Journal of Human Genetics, 2018, 63 : 289 - 296
[43] The association of HLA-C and ERAP1 polymorphisms in early and late onset psoriasis and psoriatic arthritis patients of Hungary
Kepiro, Laszlo
Szell, Marta
Kovacs, Laszlo
Keszthelyi, Peter
Kemeny, Lajos
Gyulai, Rolland
POSTEPY DERMATOLOGII I ALERGOLOGII, 2021, 38 (01): : 43 - 51
[44] Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
Skibola, Christine F.
Berndt, Sonja I.
Vijai, Joseph
Conde, Lucia
Wang, Zhaoming
Yeager, Meredith
de Bakker, Paul I. W.
Birmann, Brenda M.
Vajdic, Claire M.
Foo, Jia-Nee
Bracci, Paige M.
Vermeulen, Roel C. H.
Slager, Susan L.
de Sanjose, Silvia
Wang, Sophia S.
Linet, Martha S.
Salles, Gilles
Lan, Qing
Severi, Gianluca
Hjalgrim, Henrik
Lightfoot, Tracy
Melbye, Mads
Gu, Jian
Ghesquieres, Herve
Link, Brian K.
Morton, Lindsay M.
Holly, Elizabeth A.
Smith, Alex
Tinker, Lesley F.
Teras, Lauren R.
Kricker, Anne
Becker, Nikolaus
Purdue, Mark P.
Spinelli, John J.
Zhang, Yawei
Giles, Graham G.
Vineis, Paolo
Monnereau, Alain
Bertrand, Kimberly A.
Albanes, Demetrius
Zeleniuch-Jacquotte, Anne
Gabbas, Attilio
Chung, Charles C.
Burdett, Laurie
Hutchinson, Amy
Lawrence, Charles
Montalvan, Rebecca
Liang, Liming
Huang, Jinyan
Ma, Baoshan
AMERICAN JOURNAL OF HUMAN GENETICS, 2014, 95 (04) : 462 - 471
[45] Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia
Li, Zhiqiang
Chen, Jianhua
Yu, Hao
He, Lin
Xu, Yifeng
Zhang, Dai
Yi, Qizhong
Li, Changgui
Li, Xingwang
Shen, Jiawei
Song, Zhijian
Ji, Weidong
Wang, Meng
Zhou, Juan
Chen, Boyu
Liu, Yahui
Wang, Jiqiang
Wang, Peng
Yang, Ping
Wang, Qingzhong
Feng, Guoyin
Liu, Benxiu
Sun, Wensheng
Li, Baojie
He, Guang
Li, Weidong
Wan, Chunling
Xu, Qi
Li, Wenjin
Wen, Zujia
Liu, Ke
Huang, Fang
Ji, Jue
Ripke, Stephan
Yue, Weihua
Sullivan, Patrick F.
O'Donovan, Michael C.
Shi, Yongyong
NATURE GENETICS, 2017, 49 (11) : 1576 - +
[46] Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia
Zhiqiang Li
Jianhua Chen
Hao Yu
Lin He
Yifeng Xu
Dai Zhang
Qizhong Yi
Changgui Li
Xingwang Li
Jiawei Shen
Zhijian Song
Weidong Ji
Meng Wang
Juan Zhou
Boyu Chen
Yahui Liu
Jiqiang Wang
Peng Wang
Ping Yang
Qingzhong Wang
Guoyin Feng
Benxiu Liu
Wensheng Sun
Baojie Li
Guang He
Weidong Li
Chunling Wan
Qi Xu
Wenjin Li
Zujia Wen
Ke Liu
Fang Huang
Jue Ji
Stephan Ripke
Weihua Yue
Patrick F Sullivan
Michael C O'Donovan
Yongyong Shi
Nature Genetics, 2017, 49 : 1576 - 1583
[47] Genome-Wide Association Study for Levels of Total Serum IgE Identifies HLA-C in a Japanese Population
Yatagai, Yohei
Sakamoto, Tohru
Masuko, Hironori
Kaneko, Yoshiko
Yamada, Hideyasu
Iijima, Hiroaki
Naito, Takashi
Noguchi, Emiko
Hirota, Tomomitsu
Tamari, Mayumi
Imoto, Yoshimasa
Tokunaga, Takahiro
Fujieda, Shigeharu
Konno, Satoshi
Nishimura, Masaharu
Hizawa, Nobuyuki
PLOS ONE, 2013, 8 (12):
[48] Genome-wide association study identifies new genetic susceptibility loci for multiple primary cancers
He, Shisi
Perry, James
Li, Shengchao
Mitchell, Braxton D.
Zhang, Yuji
Chen, Shuo
Beane-Freeman, Laura
Barry, Kathryn Hughes
Berndt, Sonja I.
CANCER RESEARCH, 2024, 84 (06)
[49] Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility
Mitchell J. Machiela
Thomas G. P. Grünewald
Didier Surdez
Stephanie Reynaud
Olivier Mirabeau
Eric Karlins
Rebeca Alba Rubio
Sakina Zaidi
Sandrine Grossetete-Lalami
Stelly Ballet
Eve Lapouble
Valérie Laurence
Jean Michon
Gaelle Pierron
Heinrich Kovar
Nathalie Gaspar
Udo Kontny
Anna González-Neira
Piero Picci
Javier Alonso
Ana Patino-Garcia
Nadège Corradini
Perrine Marec Bérard
Neal D. Freedman
Nathaniel Rothman
Casey L. Dagnall
Laurie Burdett
Kristine Jones
Michelle Manning
Kathleen Wyatt
Weiyin Zhou
Meredith Yeager
David G. Cox
Robert N. Hoover
Javed Khan
Gregory T. Armstrong
Wendy M. Leisenring
Smita Bhatia
Leslie L. Robison
Andreas E. Kulozik
Jennifer Kriebel
Thomas Meitinger
Markus Metzler
Wolfgang Hartmann
Konstantin Strauch
Thomas Kirchner
Uta Dirksen
Lindsay M. Morton
Lisa Mirabello
Margaret A. Tucker
Nature Communications, 9
[50] Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis
Mells, George F.
Floyd, James A. B.
Morley, Katherine I.
Cordell, Heather J.
Franklin, Christopher S.
Shin, So-Youn
Heneghan, Michael A.
Neuberger, James M.
Donaldson, Peter T.
Day, Darren B.
Ducker, Samantha J.
Muriithi, Agnes W.
Wheater, Elizabeth F.
Hammond, Christopher J.
Dawwas, Muhammad F.
Jones, David E.
Peltonen, Leena
Alexander, Graeme J.
Sandford, Richard N.
Anderson, Carl A.
NATURE GENETICS, 2011, 43 (04) : 329 - U151

← 1 2 3 4 5 →