Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease

• Published in: Nature genetics Vol. 40; no. 10; pp. 1211 - 1215
• Main Authors: Kugathasan, Subra, Baldassano, Robert N, Bradfield, Jonathan P, Sleiman, Patrick M A, Imielinski, Marcin, Guthery, Stephen L, Cucchiara, Salvatore, Kim, Cecilia E, Frackelton, Edward C, Annaiah, Kiran, Glessner, Joseph T, Santa, Erin, Willson, Tara, Eckert, Andrew W, Bonkowski, Erin, Shaner, Julie L, Smith, Ryan M, Otieno, F George, Peterson, Nicholas, Abrams, Debra J, Chiavacci, Rosetta M, Grundmeier, Robert, Mamula, Petar, Tomer, Gitit, Piccoli, David A, Monos, Dimitri S, Annese, Vito, Denson, Lee A, Grant, Struan F A, Hakonarson, Hakon
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2008; Nature Publishing Group
• Subjects: Adolescent; Age of Onset; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Child; Child, Preschool; Children & youth; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 20 - genetics; Chromosomes, Human, Pair 21 - genetics; Cohort Studies; Data analysis; Data collection; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene Function; Genetic aspects; Genetic disorders; Genetic diversity; Genetic Linkage; Genetic Predisposition to Disease - genetics; Genetic variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Haplotypes - genetics; Hospitals; Human Genetics; Humans; Immune response; Infant; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - pathology; letter; Male; Medical sciences; Other diseases. Semiology; Polymorphism, Single Nucleotide - genetics; Quantitative trait loci; Receptors, Tumor Necrosis Factor, Member 6b - genetics; Risk Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; United States; United Kingdom; Crohn disease; Pediatrics; Digestive diseases; Intestinal disease; Locus; Inflammatory disease; Ulcerative colitis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.203

Hakon Hakonarson and colleagues report the identification of two new susceptibility loci for inflammatory bowel disease (IBD). One variant is near a gene encoding tumor necrosis factor receptor subfamily member 6B and is associated with increased levels of this protein in serum from individuals with IBD. 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 × 10 −8 and 6.95 × 10 −8 , respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10 −8 ; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.