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

Eyre, Steve, Bowes, John, Diogo, Dorothée, Lee, Annette, Barton, Anne, Martin, Paul, Zhernakova, Alexandra, Stahl, Eli, Viatte, Sebastien, McAllister, Kate, Amos, Christopher I, Padyukov, Leonid, Toes, Rene E M, Huizinga, Tom W J, Wijmenga, Cisca, Trynka, Gosia, Franke, Lude, Westra, Harm-Jan, Alfredsson, Lars, Hu, Xinli, Sandor, Cynthia, de Bakker, Paul I W, Davila, Sonia, Khor, Chiea Chuen, Heng, Khai Koon, Andrews, Robert, Edkins, Sarah, Hunt, Sarah E, Langford, Cordelia, Symmons, Deborah, Concannon, Pat, Onengut-Gumuscu, Suna, Rich, Stephen S, Deloukas, Panos, Gonzalez-Gay, Miguel A, Rodriguez-Rodriguez, Luis, Ärlsetig, Lisbeth, Martin, Javier, Rantapää-Dahlqvist, Solbritt, Plenge, Robert M, Raychaudhuri, Soumya, Klareskog, Lars, Gregersen, Peter K, Worthington, Jane, , Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate and Forbes, Alastair (2012) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nature Genetics, 44 (12). pp. 1336-40. ISSN 1061-4036

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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.

Item Type: Article
Uncontrolled Keywords: arthritis, rheumatoid,autoantibodies,chromosome mapping,european continental ancestry group,female,genetic loci,genetic predisposition to disease,genome-wide association study,humans,male,oligonucleotide array sequence analysis,polymorphism, single nucleotide
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 06 Aug 2014 10:42
Last Modified: 30 Jul 2019 14:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/49804
DOI: 10.1038/ng.2462

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