Fine mapping the TAGAP risk locus in rheumatoid arthritis

被引：32

作者：

Chen, R. ^{[1
,2
,3
]}

Stahl, E. A. ^{[1
,2
,3
]}

Kurreeman, F. A. S. ^{[1
,2
,3
,4
]}

Gregersen, P. K. ^{[5
]}

Siminovitch, K. A. ^{[6
,7
]}

Worthington, J. ^{[8
]}

Padyukov, L. ^{[9
]}

Raychaudhuri, S. ^{[1
,2
,3
]}

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

机构：

[1] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[4] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands

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

[6] Univ Hlth Network, Toronto, ON, Canada

[7] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada

[8] Univ Manchester, Arthrit Res Campaign Arc Epidemiol Unit, Manchester, Lancs, England

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

来源：

GENES AND IMMUNITY | 2011年 / 12卷 / 04期

关键词：

TAGAP; genetics; rheumatoid arthritis; GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; CELIAC-DISEASE; METAANALYSIS; IMPUTATION;

D O I：

10.1038/gene.2011.8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A common allele at the TAGAP gene locus demonstrates a suggestive, but not conclusive association with risk of rheumatoid arthritis (RA). To fine map the locus, we conducted comprehensive imputation of CEU HapMap single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) of 5500 RA cases and 22 621 controls (all of European ancestry). After controlling for population stratification with principal components analysis, the strongest signal of association was to an imputed SNP, rs212389 (P 3.9 x 10(-8), odds ratio 0.87). This SNP remained highly significant upon conditioning on the previous RA risk variant (rs394581, P = 2.2 x 10(-5)) or on a SNP previously associated with celiac disease and type I diabetes (rs1738074, P = 1.7 x 10(-4)). Our study has refined the TAGAP signal of association to a single haplotype in RA, and in doing so provides conclusive statistical evidence that the TAGAP locus is associated with RA risk. Our study also underscores the utility of comprehensive imputation in large GWAS data sets to fine map disease risk alleles. Genes and Immunity (2011) 12, 314-318; doi:10.1038/gene.2011.8; published online 10 March 2011

引用

页码：314 / 318

页数：5

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