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

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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 times 10-8 and 6.95 times 10-8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 times 10-8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.

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  1. Department of Pediatrics, Children's Research Institute and Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
  2. Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia 30322, USA.
  3. Division of Gastroenterology, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  4. Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  5. The Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  6. Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84132, USA.
  7. Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, 00185 Rome, Italy.
  8. Division of Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
  9. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
  10. Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  11. Divisions of Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  12. Divisions of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  13. Units of Gastroenterology, IRCCS, "Casa Sollievo della Sofferenza" Hospital, 71013 San Giovanni Rotondo, Italy.
  14. Units of Endoscopy, IRCCS, "Casa Sollievo della Sofferenza" Hospital, 71013 San Giovanni Rotondo, Italy.
  15. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
  16. These authors contributed equally to this work.

Correspondence to: Hakon Hakonarson5,9,15 e-mail: hakonarson@chop.edu



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