Two independent alleles at 6q23 associated with risk of rheumatoid arthritis

被引：433

作者：

Plenge, Robert M.

Cotsapas, Chris

Davies, Leela

Price, Alkes L.

Bakker, Paul I. Wde

Maller, Julian

Pe'er, Itsik

Burtt, Noel P.

Blumenstiel, Brendan

DeFelice, Matt

Parkin, Melissa

Barry, Rachel

Winslow, Wendy

Healy, Claire

Graham, Robert R.

Neale, Benjamin M.

Izmailova, Elena

Roubenoff, Ronenn

Parker, Alexander N.

Glass, Roberta

Karlson, Elizabeth W.

Maher, Nancy

Hafler, David A.

Lee, David M.

Seldin, Michael F.

Remmers, Elaine F.

Lee, Annette T.

Padyukov, Leonid

Alfredsson, Lars

Coblyn, Jonathan

Weinblatt, Michael E.

Gabriel, Stacey B.

Purcell, Shaun

Klareskog, Lars

Gregersen, Peter K.

Shadick, Nancy A.

Daly, Mark J.

Altshuler, David

机构：

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

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

[3] Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA

[5] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[6] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA

[7] Coll London, London SE5 8AF, England

[8] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA

[9] Brigham & Womens Hosp, Harvard Med Sch, Ctr Neurol Dis, Boston, MA 02115 USA

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

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

[12] N Shore Long Island Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA

[13] Karilinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

[14] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden

来源：

NATURE GENETICS | 2007年 / 39卷 / 12期

关键词：

D O I：

10.1038/ng.2007.27

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study(1). After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 ( rs10499194, similar to 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association ( GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium ( WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 ( rs6920220; P = 5 x 10(-6) in WTCCC)(2). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.

引用

页码：1477 / 1482

页数：6

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