A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

• Published in: Nature genetics Vol. 41; no. 12; pp. 1325 - 1329
• Main Authors: Asano, Kouichi, Matsushita, Tomonaga, Umeno, Junji, Hosono, Naoya, Takahashi, Atsushi, Kawaguchi, Takahisa, Matsumoto, Takayuki, Matsui, Toshiyuki, Kakuta, Yoichi, Kinouchi, Yoshitaka, Shimosegawa, Tooru, Hosokawa, Masayo, Arimura, Yoshiaki, Shinomura, Yasuhisa, Kiyohara, Yutaka, Tsunoda, Tatsuhiko, Kamatani, Naoyuki, Iida, Mitsuo, Nakamura, Yusuke, Kubo, Michiaki
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Antiporters - genetics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bowel disease; Cancer Research; Chloride-Bicarbonate Antiporters; Chromosomes, Human, Pair 13 - genetics; Colitis, Ulcerative - epidemiology; Colitis, Ulcerative - genetics; Colitis, Ulcerative - pathology; Demographic aspects; Disease Susceptibility - epidemiology; E coli; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Function; Genetic aspects; Genetic factors; Genetic Predisposition to Disease; Genetic susceptibility; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Human Genetics; Humans; Immune system; Inflammatory bowel disease; Japan; letter; Major Histocompatibility Complex - genetics; Medical sciences; Other diseases. Semiology; Polymorphism, Single Nucleotide; Population Groups; Receptors, IgG - genetics; Risk factors; Single nucleotide polymorphisms; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Ulcerative colitis; Japan; Digestive diseases; Intestinal disease; Identification; Locus; Japanese; Inflammatory disease; Ulcerative colitis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.482

Michiaki Kubo and colleagues report results of a genome-wide association study of ulcerative colitis in the Japanese population. Their study identifies three new susceptibility loci for this common inflammatory bowel disease, including FCGR2A , which has previously been implicated in other autoimmune diseases. 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 × 10 −12 ), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10 −8 ) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 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.