Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

被引：305

作者：

Radstake, Timothy R. D. J. ^{[1
]}

Gorlova, Olga ^{[2
]}

Rueda, Blanca ^{[3
]}

Martin, Jose-Ezequiel ^{[3
]}

Alizadeh, Behrooz Z. ^{[4
]}

Palomino-Morales, Rogelio ^{[3
]}

Coenen, Marieke J. ^{[5
]}

Vonk, Madelon C. ^{[1
]}

Voskuyl, Alexandre E. ^{[6
]}

Schuerwegh, Annemie J. ^{[7
]}

Broen, Jasper C. ^{[1
]}

van Riel, Piet L. C. M. ^{[1
]}

van't Slot, Ruben ^{[4
]}

Italiaander, Annet ^{[4
]}

Ophoff, Roel A. ^{[4
,8
]}

Riemekasten, Gabriela ^{[9
]}

Hunzelmann, Nico ^{[10
]}

Simeon, Carmen P. ^{[11
]}

Ortego-Centeno, Norberto ^{[12
]}

Gonzalez-Gay, Miguel A. ^{[13
]}

Gonzalez-Escribano, Maria F. ^{[14
]}

Airo, Paolo ^{[15
]}

van Laar, Jaap ^{[16
]}

Herrick, Ariane ^{[17
]}

Worthington, Jane ^{[17
]}

Hesselstrand, Roger ^{[18
]}

Smith, Vanessa

de Keyser, Filip

Houssiau, Fredric ^{[19
]}

Chee, Meng May ^{[20
]}

Madhok, Rajan ^{[20
]}

Shiels, Paul ^{[20
]}

Westhovens, Rene ^{[21
]}

Kreuter, Alexander ^{[22
]}

Kiener, Hans ^{[23
]}

de Baere, Elfride ^{[24
]}

Witte, Torsten ^{[25
]}

Padykov, Leonid ^{[26
]}

Klareskog, Lars ^{[26
]}

Beretta, Lorenzo ^{[27
]}

Scorza, Rafaella ^{[27
]}

Lie, Benedicte A. ^{[28
]}

Hoffmann-Vold, Anna-Maria ^{[29
]}

Carreira, Patricia ^{[13
,30
]}

Varga, John ^{[31
]}

Hinchcliff, Monique ^{[31
]}

Gregersen, Peter K. ^{[32
]}

Lee, Annette T. ^{[32
]}

Ying, Jun ^{[2
]}

Han, Younghun ^{[2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands

[2] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[3] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[4] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[5] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[6] Vrije Univ VU Med Ctr, Dept Rheumatol, Nijmegen, Netherlands

[7] Leiden Univ, Dept Rheumatol, Nijmegen, Netherlands

[8] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA

[9] Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany

[10] Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany

[11] Hosp Valle de Hebron, Med Interna Serv, Barcelona, Spain

[12] Hosp Clin Univ, Med Interna Serv, Granada, Spain

[13] Hosp Marques de Valdecilla, Serv Reumatol, Santander, Spain

[14] Hosp Virgen del Rocio, Serv Inmunol, Seville, Spain

[15] Univ Brescia, Brescia, Italy

[16] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[17] Univ Manchester, Manchester Acad Hlth Sci Ctr, Dept Rheumatol & Epidemiol, Manchester, Lancs, England

[18] Lund Univ, Lund, Sweden

[19] Katholieke Univ Leuven, Leuven, Belgium

[20] Univ Glasgow, Glasgow, Lanark, Scotland

[21] Univ Antwerp, B-2020 Antwerp, Belgium

[22] Ruhr Univ Bochum, Bochum, Germany

[23] Univ Vienna, Vienna, Austria

[24] Univ Ghent, Dept Genet, B-9000 Ghent, Belgium

[25] Leibniz Univ Hannover, Hannover, Germany

[26] Karolinska Inst, Stockholm, Sweden

[27] Univ Milan, Milan, Italy

[28] Oslo Univ Hosp, Rikshosp, Inst Immunol, Oslo, Norway

[29] Oslo Univ Hosp, Rikshosp, Dept Rheumatol, Oslo, Norway

[30] Hosp 12 Octubre, E-28041 Madrid, Spain

[31] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[32] Feinstein Inst Med Res, Manhasset, NY USA

[33] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA

[34] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[35] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 05期

基金：

美国国家卫生研究院;

关键词：

CD4; T-CELLS; LUPUS-ERYTHEMATOSUS; FUNCTIONAL POLYMORPHISM; JAPANESE POPULATION; CD3-ZETA EXPRESSION; COMPLEX; RISK; SCLERODERMA; MECHANISMS; PHENOTYPE;

D O I：

10.1038/ng.565

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.

引用

页码：426 / U71

页数：6

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