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 ORCID: https://orcid.org/0000-0002-8905-1052, 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, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Dunajewski, Katherine, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Fraser, Christine, Green, Elaine, Grozeva, Detelina, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Jones, Ian Richard ORCID: https://orcid.org/0000-0001-5821-5889, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 2012. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nature Genetics 44 (12) , pp. 1336-1340. 10.1038/ng.2462

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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
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Nick Craddock, Katherine Dunajewski, Valentina Escott-Price, Christine Fraser, Elaine Green, Detelina Grozeva, Marian Hamshere, Peter Holmans, Ian Jones, Michael O'Donovan and Michael Owen are collaborators on this article.
ISSN:	1061-4036
Last Modified:	15 Feb 2024 15:39
URI:	https://orca.cardiff.ac.uk/id/eprint/79123

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