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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Eyre, Steve 
Diogo, Dorothée 
Lee, Annette 
Barton, Anne 

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.

Description

Keywords

Arthritis, Rheumatoid, Autoantibodies, Chromosome Mapping, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, White People

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

44

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (076113/C/04/Z)
Wellcome Trust (091157/Z/10/B)
Wellcome Trust (091157/Z/10/Z)
CCF (None)