Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2

被引：307

作者：

Ellinghaus, Eva ^{[1
]}

Ellinghaus, David ^{[1
]}

Stuart, Philip E. ^{[2
]}

Nair, Rajan P. ^{[2
]}

Debrus, Sophie ^{[3
]}

Raelson, John V. ^{[3
]}

Belouchi, Majid ^{[3
]}

Fournier, Helene ^{[3
]}

Reinhard, Claudia ^{[3
]}

Ding, Jun ^{[4
]}

Li, Yun ^{[4
]}

Tejasvi, Trilokraj ^{[2
]}

Gudjonsson, Johann ^{[2
]}

Stoll, Stefan W. ^{[2
]}

Voorhees, John J. ^{[2
]}

Lambert, Sylviane ^{[2
]}

Weidinger, Stephan ^{[5
,6
]}

Eberlein, Bernadette ^{[5
]}

Kunz, Manfred ^{[7
]}

Rahman, Proton ^{[8
]}

Gladman, Dafna D. ^{[9
]}

Gieger, Christian ^{[10
]}

Wichmann, H. Erich ^{[10
,11
,12
]}

Karlsen, Tom H. ^{[13
]}

Mayr, Gabriele ^{[14
]}

Albrecht, Mario ^{[14
]}

Kabelitz, Dieter ^{[15
]}

Mrowietz, Ulrich ^{[6
]}

Abecasis, Goncalo R. ^{[4
]}

Elder, James T. ^{[2
,16
]}

Schreiber, Stefan ^{[1
]}

Weichenthal, Michael ^{[6
]}

Franke, Andre ^{[1
]}

机构：

[1] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

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

[3] Genizon BioSci Inc, St Laurent, PQ, Canada

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

[5] Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany

[6] Univ Kiel, Dept Dermatol, Univ Hosp Schleswig Holstein, D-2300 Kiel, Germany

[7] Univ Lubeck, Comprehens Ctr Inflammat Med, Lubeck, Germany

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

[9] Univ Toronto, Div Rheumatol, Psoriat Arthrit Program, Univ Hlth Network, Toronto, ON, Canada

[10] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany

[11] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[12] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

[13] Univ Oslo, Rikshosp, Oslo Univ Hosp, Clin Specialized Med & Surg, N-0027 Oslo, Norway

[14] Max Planck Inst Informat, Saarbrucken, Germany

[15] Univ Kiel, Inst Immunol, Univ Hosp Schleswig Holstein, Kiel, Germany

[16] Ann Arbor Vet Affairs Hosp, Ann Arbor, MI USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; T-CELL; POPULATION; GENETICS; GENES; IL12B; IL23R; POLYMORPHISMS; ACTIVATION; AUTOIMMUNE;

D O I：

10.1038/ng.689

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Psoriasis is a multifactorial skin disease characterized by epidermal hyperproliferation and chronic inflammation, the most common form of which is psoriasis vulgaris (PsV). We present a genome-wide association analysis of 2,339,118 SNPs in 472 PsV cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 PsV cases and 4,140 controls from three independent replication panels. We identified an association at TRAF3IP2 on 6q21 and genotyped two SNPs at this locus in two additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 x 10(-10) for rs13210247 and combined P = 1.24 x 10(-16) for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis (PsA). A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 x 10(-12) for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA. TRAF3IP2 encodes a protein involved in IL-17 signaling and which interacts with members of the Rel/NF-kappa B transcription factor family.

引用

页码：991 / U113

页数：7

共 37 条

[1]

The genetics of psoriasis: a complex disorder of the skin and immune system [J].

Bhalerao, J ;

Bowcock, AM .

HUMAN MOLECULAR GENETICS, 1998, 7 (10) :1537-1545

[2]

Genetics of psoriasis: The potential impact on new therapies [J].

Bowcock, AM ;

Barker, JN .

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2003, 49 (02) :S51-S56

[3]

Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis [J].

Capon, Francesca ;

Di Meglio, Paola ;

Szaub, Joanna ;

Prescott, Natalie J. ;

Dunster, Christina ;

Baumber, Laura ;

Gutin, Alexander ;

Abkevic, Victor ;

Burden, A. David ;

Lanchbury, Jerry ;

Barker, Jonathan N. ;

Trembath, Richard C. ;

Nestle, Frank O. .

HUMAN GENETICS, 2007, 122 (02) :201-206

[4]

A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes [J].

Cargill, Michele ;

Schrodi, Steven J. ;

Chang, Monica ;

Garcia, Veronica E. ;

Brandon, Rhonda ;

Callis, Kristina P. ;

Matsunami, Nori ;

Ardlie, Kristin G. ;

Civello, Daniel ;

Catanese, Joseph J. ;

Leong, Diane U. ;

Panko, Jackie M. ;

McAllister, Linda B. ;

Hansen, Christopher B. ;

Papenfuss, Jason ;

Prescott, Stephen M. ;

White, Thomas J. ;

Leppert, Mark F. ;

Krueger, Gerald G. ;

Begovich, Ann B. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (02) :273-290

[5]

Variants in the 5q31 cytokine gene cluster are associated with psoriasis [J].

Chang, M. ;

Li, Y. ;

Yan, C. ;

Callis-Duffin, K. P. ;

Matsunami, N. ;

Garcia, V. E. ;

Cargill, M. ;

Civello, D. ;

Bui, N. ;

Catanese, J. J. ;

Leppert, M. F. ;

Krueger, G. G. ;

Begovich, A. B. ;

Schrodi, S. J. .

GENES AND IMMUNITY, 2008, 9 (02) :176-181

[6]

Activation of NF-κB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-κB-inducing kinase -: Identification of a novel TRAF6 interaction motif [J].

Darnay, BG ;

Ni, J ;

Moore, PA ;

Aggarwal, BB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (12) :7724-7731

[7]

Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis [J].

de Cid, Rafael ;

Riveira-Munoz, Eva ;

Zeeuwen, Patrick L. J. M. ;

Robarge, Jason ;

Liao, Wilson ;

Dannhauser, Emma N. ;

Giardina, Emiliano ;

Stuart, Philip E. ;

Nair, Rajan ;

Helms, Cynthia ;

Escaramis, Georgia ;

Ballana, Ester ;

Martin-Ezquerra, Gemma ;

den Heijer, Martin ;

Kamsteeg, Marijke ;

Joosten, Irma ;

Eichler, Evan E. ;

Lazaro, Conxi ;

Pujol, Ramon M. ;

Armengol, Lluis ;

Abecasis, Goncalo ;

Elder, James T. ;

Novelli, Giuseppe ;

Armour, John A. L. ;

Kwok, Pui-Yan ;

Bowcock, Anne ;

Schalkwijk, Joost ;

Estivill, Xavier .

NATURE GENETICS, 2009, 41 (02) :211-215

[8]

PS power and sample size program available for free on the Internet [J].

Dupont, WD ;

Plummer, WD .

CONTROLLED CLINICAL TRIALS, 1997, 18 (03) :274-274

[9]

THE GENETICS OF PSORIASIS [J].

ELDER, JT ;

NAIR, RP ;

GUO, SW ;

HENSELER, T ;

CHRISTOPHERS, E ;

VOORHEES, JJ .

ARCHIVES OF DERMATOLOGY, 1994, 130 (02) :216-224

[10]

A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

← 1 2 3 4 →