Common variants at CD40 and other loci confer risk of rheumatoid arthritis

被引：431

作者：

Raychaudhuri, Soumya ^{[1
,2
,3
,4
]}

Remmers, Elaine F. ^{[5
]}

Lee, Annette T. ^{[6
]}

Hackett, Rachel ^{[1
,2
]}

Guiducci, Candace ^{[1
,2
]}

Burtt, Noel P. ^{[1
,2
]}

Gianniny, Lauren ^{[1
,2
]}

Korman, Benjamin D. ^{[5
]}

Padyukov, Leonid ^{[7
]}

Kurreeman, Fina A. S. ^{[8
]}

Chang, Monica ^{[9
]}

Catanese, Joseph J. ^{[9
]}

Ding, Bo ^{[10
]}

Wong, Sandra ^{[1
,2
]}

Mil, Annette H. M. van der Helm-van ^{[8
]}

Neale, Benjamin M. ^{[1
,2
,4
,11
]}

Coblyn, Jonathan ^{[3
]}

Cui, Jing ^{[3
]}

Tak, Paul P. ^{[12
]}

Wolbink, Gert Jan ^{[13
,14
]}

Crusius, J. Bart A. ^{[16
]}

van der Horst-Bruinsma, Irene E. ^{[15
]}

Criswell, Lindsey A. ^{[17
]}

Amos, Christopher I. ^{[18
]}

Seldin, Michael F. ^{[19
]}

Kastner, Daniel L. ^{[5
]}

Ardlie, Kristin G. ^{[1
,2
,20
]}

Alfredsson, Lars ^{[10
]}

Costenbader, Karen H. ^{[3
]}

Altshuler, David ^{[1
,2
,4
]}

Huizinga, Tom W. J. ^{[8
]}

Shadick, Nancy A. ^{[3
]}

Weinblatt, Michael E. ^{[3
]}

de Vries, Niek

Worthington, Jane ^{[21
]}

Seielstad, Mark ^{[22
]}

Toes, Rene E. M. ^{[8
]}

Karlson, Elizabeth W. ^{[3
]}

Begovich, Ann B. ^{[9
]}

Klareskog, Lars ^{[7
]}

Gregersen, Peter K. ^{[6
]}

Daly, Mark J. ^{[1
,2
,4
]}

Plenge, Robert M. ^{[1
,2
,3
,4
]}

机构：

[1] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

[2] MIT, Cambridge, MA 02142 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[5] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA

[6] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA

[7] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden

[8] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2333 ZA Leiden, Netherlands

[9] Celera, Alameda, CA 94502 USA

[10] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden

[11] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England

[12] Univ Amsterdam, Acad Med Ctr, NL-326 Amsterdam, Netherlands

[13] Jan van Breemen Inst, NL-1056 AB Amsterdam, Netherlands

[14] Univ Amsterdam, Acad Med Ctr, Sanquin Res Landsteiner Lab, NL-1006 AD Amsterdam, Netherlands

[15] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, NL-1007 MB Amsterdam, Netherlands

[16] Vrije Univ Amsterdam, Med Ctr, Immunogenet Lab, Dept Pathol, NL-1007 MB Amsterdam, Netherlands

[17] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA

[18] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[19] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA

[20] SeraCare Life Sci, Cambridge, MA 02139 USA

[21] Univ Manchester, Arthrit Res Campaign Epidemiol Unit, Manchester M13 9PT, Lancs, England

[22] Genome Inst Singapore, Singapore 138672, Singapore

来源：

NATURE GENETICS | 2008年 / 40卷 / 10期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

D O I：

10.1038/ng.233

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls(1,2). We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).

引用

页码：1216 / 1223

页数：8

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