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

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