title: Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.
abstract: To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10(-800)), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes ANTXR2 (rs4333130; P = 9.3 x 10(-8)) and IL1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 x 10(-14)) and ERAP1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.
authors.affiliation: University of Texas Health Science Center at Houston, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Sims
authors.forename: Patrick
authors.initials: P
authors.lastname: Danoy
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Paul
authors.initials: P
authors.lastname: Leo
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bradbury
authors.forename: Louise H
authors.initials: LH
authors.lastname: Appleton
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.forename: Laura
authors.initials: L
authors.lastname: Diekman
authors.forename: Tracey
authors.initials: T
authors.lastname: Doan
authors.forename: Alison
authors.initials: A
authors.lastname: Dowling
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.forename: Emma L
authors.initials: EL
authors.lastname: Duncan
authors.forename: Claire
authors.initials: C
authors.lastname: Farrar
authors.forename: Johanna
authors.initials: J
authors.lastname: Hadler
authors.forename: David
authors.initials: D
authors.lastname: Harvey
authors.forename: Tugce
authors.initials: T
authors.lastname: Karaderi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mogg
authors.forename: Emma
authors.initials: E
authors.lastname: Pomeroy
authors.forename: Karena
authors.initials: K
authors.lastname: Pryce
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Taylor
authors.forename: Laurie
authors.initials: L
authors.lastname: Savage
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Vasudev
authors.initials: V
authors.lastname: Kumanduri
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Sue M
authors.initials: SM
authors.lastname: Ring
authors.forename: Pamela
authors.initials: P
authors.lastname: Whittaker
authors.forename: Evgeny
authors.initials: E
authors.lastname: Glazov
authors.forename: Gethin P
authors.initials: GP
authors.lastname: Thomas
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ward
authors.forename: Millicent A
authors.initials: MA
authors.lastname: Stone
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D015331:Cohort Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013167:Spondylitis, Ankylosing / Q000235:genetics*