Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

被引：1191

作者：

Nair, Rajan P. ^{[1
]}

Duffin, Kristina Callis ^{[2
]}

Helms, Cynthia ^{[3
]}

Ding, Jun ^{[4
]}

Stuart, Philip E. ^{[1
]}

Goldgar, David ^{[2
]}

Gudjonsson, Johann E. ^{[1
]}

Li, Yun

Tejasvi, Trilokraj ^{[1
]}

Feng, Bing-Jian ^{[2
]}

Ruether, Andreas ^{[5
]}

Schreiber, Stefan ^{[5
]}

Weichenthal, Michael ^{[6
]}

Gladman, Dafna ^{[7
]}

Rahman, Proton ^{[8
]}

Schrodi, Steven J. ^{[9
]}

Prahalad, Sampath ^{[10
,11
,12
]}

Guthery, Stephen L. ^{[10
,11
,12
]}

Fischer, Judith ^{[13
]}

Liao, Wilson

Kwok, Pui-Yan ^{[14
]}

Menter, Alan ^{[15
]}

Lathrop, G. Mark ^{[13
]}

Awise, Carol ^{[16
]}

Begovich, Ann B.

Voorhees, John J. ^{[1
]}

Elder, James T. ^{[1
,17
]}

Krueger, Gerald G. ^{[2
]}

Bowcock, Anne M. ^{[3
]}

Abecasis, Goncalo R. ^{[4
]}

机构：

[1] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

[2] Univ Utah, Dept Dermatol, Salt Lake City, UT 84131 USA

[3] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA

[4] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[5] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[6] Univ Kiel, Dept Dermatol, D-24105 Kiel, Germany

[7] Univ Toronto, Dept Rheumatol, Toronto, ON M5T 2S8, Canada

[8] Mem Univ Newfoundland, Dept Med, St John, NF A1C 5B8, Canada

[9] Celera, Alameda, CA 94502 USA

[10] Univ Utah, Dept Pediat, Salt Lake City, UT 84312 USA

[11] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[12] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA

[13] Ctr Natl Genotypage, Inst Genom, F-91057 Evry, France

[14] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94153 USA

[15] Baylor Univ, Med Ctr, Dept Dermatol, Dallas, TX 75246 USA

[16] Texas Scottish Rite Hosp Children, Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA

[17] Ann Arbor Vet Affairs Hosp, Ann Arbor, MI 48105 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

基金：

美国国家卫生研究院;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL; GENETIC-ASSOCIATION; VARIANTS; SUSCEPTIBILITY; IDENTIFICATION; MULTIPLE; DISEASE; RISK; PATHOGENESIS;

D O I：

10.1038/ng.311

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappa B signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.

引用

页码：199 / 204

页数：6

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