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

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ID: 4987
2012
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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.
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eyre2012highdensitynature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors 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;
Journal nature genetics
Year 2012
DOI
10.1038/ng.2462
URL
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