title: Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.
authors.affiliation: Department of Pediatrics, Children's Research Institute and Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Guthery
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: Kiran
authors.initials: K
authors.lastname: Annaiah
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Erin
authors.initials: E
authors.lastname: Santa
authors.forename: Tara
authors.initials: T
authors.lastname: Willson
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Eckert
authors.forename: Erin
authors.initials: E
authors.lastname: Bonkowski
authors.forename: Julie L
authors.initials: JL
authors.lastname: Shaner
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Smith
authors.forename: F George
authors.initials: FG
authors.lastname: Otieno
authors.forename: Nicholas
authors.initials: N
authors.lastname: Peterson
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Abrams
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Robert
authors.initials: R
authors.lastname: Grundmeier
authors.forename: Petar
authors.initials: P
authors.lastname: Mamula
authors.forename: Gitit
authors.initials: G
authors.lastname: Tomer
authors.forename: David A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: Dimitri S
authors.initials: DS
authors.lastname: Monos
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson