@article{0077264ab548466c8ddb60bab7859c43,
title = "Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease",
abstract = "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.",
author = "Subra Kugathasan and Baldassano, {Robert N.} and Bradfield, {Jonathan P.} and Sleiman, {Patrick M.A.} and Marcin Imielinski and Guthery, {Stephen L.} and Salvatore Cucchiara and Kim, {Cecilia E.} and Frackelton, {Edward C.} and Kiran Annaiah and Glessner, {Joseph T.} and Erin Santa and Tara Willson and Eckert, {Andrew W.} and Erin Bonkowski and Shaner, {Julie L.} and Smith, {Ryan M.} and Otieno, {F. George} and Nicholas Peterson and Abrams, {Debra J.} and Chiavacci, {Rosetta M.} and Robert Grundmeier and Petar Mamula and Gitit Tomer and Piccoli, {David A.} and Monos, {Dimitri S.} and Vito Annese and Denson, {Lee A.} and Grant, {Struan F.A.} and Hakon Hakonarson",
note = "Funding Information: We would like to thank all participating subjects and families. We thank M. Garris, K. Thomas, A. Albano, E. Dabaghyan, K. Fain, W. Glaberson, K. Harden, A. Hill, C. Johnson-Honesty, L. McCleery, K. Lake, R. Bezold, A. Ryan, A. Thomas, A. Latiano and R. Skraban for their expert assistance with DNA processing, genotyping, RNA preparation, DCR3 ELISA, data collection or study management. We thank A. Rutherford and J. Nebel for study coordination. We also thank S. Kristinsson, L. Arni Hermannsson and A. Krisbj{\"o}rnsson of Raf{\"o}rninn ehf for their extensive software design and informatics contribution. This research was financially supported by US National Institutes of Health grant (K23RR016111), Crohn{\textquoteright}s & Colitis Foundation of America (CCFA), The Koss foundation, the NIH General Clinical Research Center of the Medical College of Wisconsin (S.K.), NIH grant R01 DK058259, the CCFA (L.D.), the Primary Children{\textquoteright}s Medical Center Foundation, K23DK069513, M01-RR00064, C06-RR11234 from the National Center for Research Resources (S.L.G.), the Edmunds Fund, the Heineman Foundation, the IBD Family Research Council (R.B.), a Research Development Award from the Cotswold Foundation (H.H. and S.F.A.G.) and a CTSA award, UL1-RR024134-03 (H.H.). Colon microarray experiments were performed and analyzed in the Microarray and Bioinformatics Cores of the NIH-supported Cincinnati Children{\textquoteright}s Hospital Research Foundation Digestive Health Center (1P30DK078392-01). H. Xu of the Bioinformatics Core assisted with analysis of the microarray experiments. All genotyping and other aspects of the study were funded by an Institute Development Award (H.H., S.F.A.G.) from the Children{\textquoteright}s Hospital of Philadelphia. We thank the members of the International HapMap and Wellcome Trust Case Control Consortiums for publicly providing valuable data, which were crucial for part of our analyses.",
year = "2008",
month = oct,
doi = "10.1038/ng.203",
language = "English (US)",
volume = "40",
pages = "1211--1215",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",
}