TY - JOUR
T1 - High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis
AU - Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate
AU - Wellcome Trust Case-Control Consortium
AU - The Biologics in RA Genetics and Genomics (BRAGGS)
AU - Breast Cancer Susceptibility Collaboration (UK)
AU - Eyre, Steve
AU - Bowes, John
AU - Diogo, Dorothée
AU - Lee, Annette
AU - Barton, Anne
AU - Martin, Paul
AU - Zhernakova, Alexandra
AU - Stahl, Eli
AU - Viatte, Sebastien
AU - McAllister, Kate
AU - Amos, Christopher I.
AU - Padyukov, Leonid
AU - Toes, Rene E.M.
AU - Huizinga, Tom W.J.
AU - Wijmenga, Cisca
AU - Trynka, Gosia
AU - Franke, Lude
AU - Westra, Harm Jan
AU - Alfredsson, Lars
AU - Hu, Xinli
AU - Sandor, Cynthia
AU - De Bakker, Paul I.W.
AU - Davila, Sonia
AU - Khor, Chiea Chuen
AU - Heng, Khai Koon
AU - Andrews, Robert
AU - Edkins, Sarah
AU - Hunt, Sarah E.
AU - Langford, Cordelia
AU - Symmons, Deborah P.M.
AU - Concannon, Pat
AU - Onengut-Gumuscu, Suna
AU - Rich, Stephen S.
AU - Deloukas, Panos
AU - Gonzalez-Gay, Miguel A.
AU - Rodriguez-Rodriguez, Luis
AU - Ärlsetig, Lisbeth
AU - Martin, Javier
AU - Rantapää-Dahlqvist, Solbritt
AU - Plenge, Robert M.
AU - Raychaudhuri, Soumya
AU - Klareskog, Lars
AU - Gregersen, Peter K.
AU - Worthington, Jane
AU - Moitra, R. K.
AU - Prouse, P. J.
AU - Shawe, D. J.
AU - Crisp, A. J.
AU - Gaston, J. S.H.
AU - Ng, W. F.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84870531924
U2 - 10.1038/ng.2462
DO - 10.1038/ng.2462
M3 - Article
C2 - 23143596
AN - SCOPUS:84870531924
SN - 1061-4036
VL - 44
SP - 1336
EP - 1340
JO - Nature Genetics
JF - Nature Genetics
IS - 12
ER -