title: A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population.
abstract: Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Yokohama, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Asano
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Matsushita
authors.forename: Junji
authors.initials: J
authors.lastname: Umeno
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsui
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: Masayo
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Arimura
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
mesh_terms: D017920:Antiporters / Q000235:genetics; D044466:Asian People / Q000235:genetics; D027963:Chloride-Bicarbonate Antiporters; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004198:Disease Susceptibility / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008285:Major Histocompatibility Complex / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups; D017452:Receptors, IgG / Q000235:genetics; D000076988:Sulfate Transporters
chemical_list: D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; C445323:FCGR2A protein, human; D017452:Receptors, IgG; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters