Letter abstract
Nature Genetics 40, 1211 - 1215 (2008)
Published online: 31 August 2008 | doi:10.1038/ng.203
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease
Subra Kugathasan1,2,16, Robert N Baldassano3,4,16, Jonathan P Bradfield5, Patrick M A Sleiman5, Marcin Imielinski5, Stephen L Guthery6, Salvatore Cucchiara7, Cecilia E Kim5, Edward C Frackelton5, Kiran Annaiah5, Joseph T Glessner5, Erin Santa5, Tara Willson8, Andrew W Eckert5, Erin Bonkowski8, Julie L Shaner5, Ryan M Smith5, F George Otieno5, Nicholas Peterson1, Debra J Abrams3,4, Rosetta M Chiavacci5, Robert Grundmeier9,10, Petar Mamula3,4, Gitit Tomer8, David A Piccoli3,4, Dimitri S Monos11,12, Vito Annese13,14, Lee A Denson8, Struan F A Grant5,9,15 & Hakon Hakonarson5,9,15
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.
- Department of Pediatrics, Children's Research Institute and Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
- Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia 30322, USA.
- Division of Gastroenterology, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- The Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84132, USA.
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, 00185 Rome, Italy.
- Division of Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
- Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
- Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- Divisions of Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- Divisions of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- Units of Gastroenterology, IRCCS, "Casa Sollievo della Sofferenza" Hospital, 71013 San Giovanni Rotondo, Italy.
- Units of Endoscopy, IRCCS, "Casa Sollievo della Sofferenza" Hospital, 71013 San Giovanni Rotondo, Italy.
- Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
- These authors contributed equally to this work.
Correspondence to: Hakon Hakonarson5,9,15 e-mail: hakonarson@chop.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
New susceptibility genes for ulcerative colitisNature Genetics News and Views (01 Jun 2008)
RESEARCH
Investigation of Reported Associations Between the 20q13 and 21q22 Loci and Pediatric-Onset Crohn's Disease in Canadian ChildrenThe American Journal of Gastroenterology Article Response
Ulcerative colitis?risk loci on chromosomes 1p36 and 12q15 found by genome-wide association studyNature Genetics Letter (01 Feb 2009)
An SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29Genes and Immunity Original Article
See all 43 matches for Research
