title: REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
abstract: We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 x 10(-10)). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 x 10(-14)) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 x 10(-11)) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 x 10(-9)) and BLK (rs2736340; OR = 1.19; P = 5.69 x 10(-9)). c-Rel is an NF-kappaB family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Chistopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Sokka
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.forename: S Louis
authors.initials: SL
authors.lastname: Bridges
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D020573:Genes, rel; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide