Fine mapping the TAGAP risk locus in rheumatoid arthritis

R. Chen, E. A. Stahl, F. A.S. Kurreeman, P. K. Gregersen, K. A. Siminovitch, J. Worthington, L. Padyukov, S. Raychaudhuri, R. M. Plenge

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 (P3.9 × 10 -8, odds ratio0.87). This SNP remained highly significant upon conditioning on the previous RA risk variant (rs394581, P2.2 × 10 -5) or on a SNP previously associated with celiac disease and type I diabetes (rs1738074, P1.7 × 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.

Original languageEnglish
Pages (from-to)314-318
Number of pages5
JournalGenes and Immunity
Volume12
Issue number4
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • TAGAP
  • genetics
  • rheumatoid arthritis

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