Two independent alleles at 6q23 associated with risk of rheumatoid arthritis

This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association an...

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Published in:	Nature genetics Vol. 39; no. 12; pp. 1477 - 1482
Main Authors:	Plenge, Robert M, Cotsapas, Chris, Davies, Leela, Price, Alkes L, de Bakker, Paul I W, Maller, Julian, Pe'er, Itsik, Burtt, Noel P, Blumenstiel, Brendan, DeFelice, Matt, Parkin, Melissa, Barry, Rachel, Winslow, Wendy, Healy, Claire, Graham, Robert R, Neale, Benjamin M, Izmailova, Elena, Roubenoff, Ronenn, Parker, Alexander N, Glass, Roberta, Karlson, Elizabeth W, Maher, Nancy, Hafler, David A, Lee, David M, Seldin, Michael F, Remmers, Elaine F, Lee, Annette T, Padyukov, Leonid, Alfredsson, Lars, Coblyn, Jonathan, Weinblatt, Michael E, Gabriel, Stacey B, Purcell, Shaun, Klareskog, Lars, Gregersen, Peter K, Shadick, Nancy A, Daly, Mark J, Altshuler, David
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.12.2007 Nature Publishing Group
Subjects:	Agriculture Alleles Animal Genetics and Genomics Arthritis, Rheumatoid - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Case-Control Studies Chromosomes, Human, Pair 6 Classical genetics, quantitative genetics, hybrids Diagnosis Diseases of the osteoarticular system Female Fundamental and applied biological sciences. Psychology Gene Function Gene loci Genetic aspects Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Genome, Human Genotype & phenotype Haplotypes Health risk assessment Human Genetics Humans Inflammatory joint diseases letter Male Medical research Medical sciences Methods, theories and miscellaneous Physiological aspects Polymorphism, Single Nucleotide Rheumatoid arthritis Risk factors Single nucleotide polymorphisms United States Genetic mapping Immunopathology Allele Chronic Rheumatoid arthritis Diseases of the osteoarticular system Autoimmune disease Risk Inflammatory joint disease
ISSN:	1061-4036, 1546-1718, 1546-1718
Online Access:	Get full text
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Summary:	This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study 1 . After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, ∼150 kb from TNFAIP3 and OLIG3 ) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples ( P = 10 −3 , GWA scan; P < 10 −6 , replication; P = 10 −9 , combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 × 10 −6 in WTCCC) 2 . We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.2007.27