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High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.
Nat Genet 2012; 44(12):1336-40NGen

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.

Authors+Show Affiliations

Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23143596

Citation

Eyre, Steve, et al. "High-density Genetic Mapping Identifies New Susceptibility Loci for Rheumatoid Arthritis." Nature Genetics, vol. 44, no. 12, 2012, pp. 1336-40.
Eyre S, Bowes J, Diogo D, et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012;44(12):1336-40.
Eyre, S., Bowes, J., Diogo, D., Lee, A., Barton, A., Martin, P., ... Worthington, J. (2012). High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nature Genetics, 44(12), pp. 1336-40. doi:10.1038/ng.2462.
Eyre S, et al. High-density Genetic Mapping Identifies New Susceptibility Loci for Rheumatoid Arthritis. Nat Genet. 2012;44(12):1336-40. PubMed PMID: 23143596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. 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, AU - ,, AU - ,, 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, Y1 - 2012/11/11/ PY - 2012/05/10/received PY - 2012/10/10/accepted PY - 2012/11/13/entrez PY - 2012/11/13/pubmed PY - 2013/2/14/medline SP - 1336 EP - 40 JF - Nature genetics JO - Nat. Genet. VL - 44 IS - 12 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. SN - 1546-1718 UR - https://www.unboundmedicine.com/medline/citation/23143596/High_density_genetic_mapping_identifies_new_susceptibility_loci_for_rheumatoid_arthritis_ DB - PRIME DP - Unbound Medicine ER -