title: Two independent alleles at 6q23 associated with risk of rheumatoid arthritis.
abstract: 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. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 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 x 10(-6) in WTCCC). 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.
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. rplenge@partners.org
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: Chris
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authors.lastname: Cotsapas
authors.forename: Leela
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authors.lastname: Davies
authors.forename: Alkes L
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authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Julian
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authors.lastname: Maller
authors.forename: Itsik
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authors.forename: Noel P
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authors.forename: Brendan
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authors.lastname: DeFelice
authors.forename: Melissa
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authors.lastname: Parkin
authors.forename: Rachel
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authors.lastname: Barry
authors.forename: Wendy
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authors.lastname: Winslow
authors.forename: Claire
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authors.lastname: Healy
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authors.initials: RR
authors.lastname: Graham
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Neale
authors.forename: Elena
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authors.lastname: Izmailova
authors.forename: Ronenn
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authors.lastname: Roubenoff
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Parker
authors.forename: Roberta
authors.initials: R
authors.lastname: Glass
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Nancy
authors.initials: N
authors.lastname: Maher
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Leonid
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authors.lastname: Padyukov
authors.forename: Lars
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authors.lastname: Alfredsson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coblyn
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Shadick
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide