High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, Wellcome Trust Case Control Consortium, The Biologics in RA Genetics and Genomics (BRAGGS), Breast Cancer Susceptibility Collaboration (UK)

Research output: Contribution to journalArticlepeer-review

508 Scopus citations

Abstract

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

Original languageEnglish
Pages (from-to)1336-1340
Number of pages5
JournalNature Genetics
Volume44
Issue number12
DOIs
StatePublished - 1 Dec 2012
Externally publishedYes

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