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Pediatric Inflammatory Bowel Disease pp 3–12Cite as

Genetics of Inflammatory Bowel Diseases

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Abstract

The inflammatory bowel diseases (IBD), Crohn disease and ulcerative colitis, are immune-mediated disorders resulting in chronic, relapsing inflammation of the gastrointestinal tract. The complex nature of IBD supports the notion that its origin is likely multifactorial, constituting both genes and environmental factors. It has been hypothesized that environmental factors and maladaptive immune responses to gastrointestinal flora generate a dysregulated inflammatory cascade creating mucosal injury in genetically susceptible individuals. Over the last decade, considerable interest and research has focused on the genetic aspect of IBD. The identification of linkage between Crohn disease and the pericentromeric region of chromosome 16 (IBD1) by Hugot in 1996 spawned a series of genome scans and linkage analyses in search of susceptibility and phenotypic modifier genes (Nature 379:821–3, 1996). In 2001, the discovery that specific polymorphisms in the CARD15/NOD2 gene at the IBD1 locus were associated with Crohn disease engendered a new era of genotype–phenotype investigations (Nature 411:599–603, 2001; Nature 411:603–6, 2001). The advent of genome-wide association studies has resulted in the successful identification of new, well-replicated disease associations. The heterogeneity of IBD phenotypes suggests that it is a polygenic disorder in which susceptibility loci act in epistasis with other disease-modifying genes and the environment to produce disease. Understanding genetic associations of IBD can provide patients and their families with useful information that may help them cope with the disease. Furthermore, as our knowledge of genotype–phenotype associations grows, it is anticipated that genotyping at the onset of disease may enable physicians to predict disease course and tailor medical therapies specific for each patient.

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References

  1. Hugot JP, Laurent-Puig P, Gower-Rousseau C, et al. Mapping of a susceptibility locus for Crohn’s disease on chromosome 16. Nature. 1996;379:821–3.

    Article  PubMed  CAS  Google Scholar 

  2. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.

    Article  PubMed  CAS  Google Scholar 

  3. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–6.

    Article  PubMed  CAS  Google Scholar 

  4. Duerr RH. The genetics of inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31:63–76.

    Article  PubMed  Google Scholar 

  5. Basu D, Lopez I, Kulkarni A, Sellin JH. Impact of race and ­ethnicity on inflammatory bowel disease. Am J Gastroenterol. 2005;100:2254–61.

    Article  PubMed  Google Scholar 

  6. Weinstein TA, Levine M, Pettei MJ, Gold DM, Kessler BH, Levine JJ. Age and family history at presentation of pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2003;37:609–13.

    Article  PubMed  Google Scholar 

  7. Laharie D, Debeugny S, Peeters M, et al. Inflammatory bowel disease in spouses and their offspring. Gastroenterology. 2001;120:816–9.

    Article  PubMed  CAS  Google Scholar 

  8. Orholm M, Fonager K, Sorensen HT. Risk of ulcerative colitis and Crohn’s disease among offspring of patients with chronic inflammatory bowel disease. Am J Gastroenterol. 1999;94:3236–8.

    Article  PubMed  CAS  Google Scholar 

  9. Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO. Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol. 2000;35:1075–81.

    Article  PubMed  CAS  Google Scholar 

  10. Thompson NP, Driscoll R, Pounder RE, Wakefield AJ. Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ. 1996;312:95–6.

    Article  PubMed  CAS  Google Scholar 

  11. Tysk C, Lindberg E, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988;29:990–6.

    Article  PubMed  CAS  Google Scholar 

  12. Brant S. Update on the heritability of inflammatory bowel disease: the importance of twin studies. Inflamm Bowel Dis. 2011;17:1–5.

    Article  PubMed  Google Scholar 

  13. Lesage S, Zouali H, Cezard JP, et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002;70:845–57.

    Article  PubMed  CAS  Google Scholar 

  14. Pauleau AL, Murray PJ. Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol. 2003;23:7531–9.

    Article  PubMed  CAS  Google Scholar 

  15. Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731–4.

    Article  PubMed  CAS  Google Scholar 

  16. Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP. Differential effects of NOD2 variants on Crohn’s disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol. 2004;99:2393–404.

    Article  PubMed  CAS  Google Scholar 

  17. Cummings JR, Jewell DP. Clinical implications of inflammatory bowel disease genetics on phenotype. Inflamm Bowel Dis. 2005;11:56–61.

    Article  PubMed  Google Scholar 

  18. Kugathasan S, Loizides A, Babusukumar U, et al. Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn’s disease. Inflamm Bowel Dis. 2005;11:631–8.

    Article  PubMed  Google Scholar 

  19. Weiss B, Shamir R, Bujanover Y, et al. NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared with adults with Crohn’s disease. J Pediatr. 2004;145:208–12.

    Article  PubMed  CAS  Google Scholar 

  20. Latiano A, Palmieri O, Valvano RM, et al. Contribution of IBD5 locus to clinical features of IBD patients. Am J Gastroenterol. 2006;101:318–25.

    Article  PubMed  CAS  Google Scholar 

  21. Noble CL, Nimmo ER, Drummond H, et al. The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn’s disease. Gastroenterology. 2005;129:1854–64.

    Article  PubMed  CAS  Google Scholar 

  22. Yamazaki K, Takazoe M, Tanaka T, et al. Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. J Hum Genet. 2004;49:664–8.

    Article  PubMed  CAS  Google Scholar 

  23. Newman B, Gu X, Wintle R, et al. A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn’s disease. Gastroenterology. 2005;128:260–9.

    Article  PubMed  CAS  Google Scholar 

  24. Peltekova VD, Wintle RF, Rubin LA, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004;36:471–5.

    Article  PubMed  CAS  Google Scholar 

  25. Pierik M, Yang H, Barmada MM, et al. The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction. Inflamm Bowel Dis. 2005;11:1–7.

    Article  PubMed  Google Scholar 

  26. Armuzzi A, Ahmad T, Ling KL, et al. Genotype-phenotype analysis of the Crohn’s disease susceptibility haplotype on chromosome 5q31. Gut. 2003;52:1133–9.

    Article  PubMed  CAS  Google Scholar 

  27. Torok HP, Glas J, Tonenchi L, et al. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn’s disease. Gut. 2005;54:1421–7.

    Article  PubMed  Google Scholar 

  28. Palmieri O, Latiano A, Valvano R, et al. Variants of OCTN1-2 cation transporter genes are associated with both Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2006;23:497–506.

    Article  PubMed  CAS  Google Scholar 

  29. Russell RK, Drummond HE, Nimmo ER, et al. Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut. 2006;55:1114–23.

    Article  PubMed  CAS  Google Scholar 

  30. Babusukumar U, Wang T, McGuire E, Broeckel U, Kugathasan S. Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn’s disease. Am J Gastroenterol. 2006;101:1354–61.

    Article  PubMed  CAS  Google Scholar 

  31. Silverberg MS, Duerr RH, Brant SR, et al. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn’s disease. Eur J Hum Genet. 2007;15:328–35.

    Article  PubMed  CAS  Google Scholar 

  32. Stoll M, Corneliussen B, Costello CM, et al. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet. 2004;36:476–80.

    Article  PubMed  CAS  Google Scholar 

  33. Buning C, Geerdts L, Fiedler T, et al. DLG5 variants in inflammatory bowel disease. Am J Gastroenterol. 2006;101:786–92.

    Article  PubMed  Google Scholar 

  34. Ahmad T, Marshall S, Jewell D. Genotype-based phenotyping heralds a new taxonomy for inflammatory bowel disease. Curr Opin Gastroenterol. 2003;19:327–35.

    Article  PubMed  CAS  Google Scholar 

  35. Stokkers PC, Reitsma PH, Tytgat GN, van Deventer SJ. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta- analysis. Gut. 1999;45:395–401.

    Article  PubMed  CAS  Google Scholar 

  36. Silverberg MS, Mirea L, Bull SB, et al. A population- and family-based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease. Inflamm Bowel Dis. 2003;9:1–9.

    Article  PubMed  Google Scholar 

  37. Orchard TR, Chua CN, Ahmad T, Cheng H, Welsh KI, Jewell DP. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology. 2002;123:714–8.

    Article  PubMed  Google Scholar 

  38. Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology. 2000;118:274–8.

    Article  PubMed  CAS  Google Scholar 

  39. Yap LM, Ahmad T, Jewell DP. The contribution of HLA genes to IBD susceptibility and phenotype. Best Pract Res. 2004;18:577–96.

    Article  CAS  Google Scholar 

  40. Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.

    Article  PubMed  CAS  Google Scholar 

  41. Van Limbergen JE, Russell RK, Nimmo ER, et al. IL23R Arg381Gln is associated with childhood onset inflammatory bowel disease in Scotland. Gut. 2007;56(8):1173–4.

    Article  PubMed  Google Scholar 

  42. Libioulle C, Louis E, Hansoul S, et al. A novel susceptibility locus for Crohn’s disease identified by whole genome association maps to a gene desert on chromosome 5p13.1 and modulates the level of expression of the prostaglandin receptor EP4. PLoS Genet. 2007;3(4):e58.

    Article  PubMed  Google Scholar 

  43. Parham C, Chirica M, Timans J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168:5699–708.

    PubMed  CAS  Google Scholar 

  44. Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006;203:2473–83.

    Article  PubMed  CAS  Google Scholar 

  45. Kullberg MC, Jankovic D, Feng CG, et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med. 2006;203:2485–94.

    Article  PubMed  CAS  Google Scholar 

  46. Uhlig HH, McKenzie BS, Hue S, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006;25:309–18.

    Article  PubMed  CAS  Google Scholar 

  47. Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–6.

    Article  PubMed  CAS  Google Scholar 

  48. Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8.

    Article  PubMed  CAS  Google Scholar 

  49. Cargill M, Schrodi SJ, Chang M, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet. 2007;80:273–90.

    Article  PubMed  CAS  Google Scholar 

  50. Mannon PJ, Fuss IJ, Mayer L, et al. Anti-interleukin-12 antibody for active Crohn’s disease. N Engl J Med. 2004;351:2069–79.

    Article  PubMed  CAS  Google Scholar 

  51. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends Immunol. 2006;27:17–23.

    Article  PubMed  CAS  Google Scholar 

  52. Hampe J, Franke A, Rosenstiel P, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.

    Article  PubMed  CAS  Google Scholar 

  53. Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39(5):596–604.

    Article  PubMed  CAS  Google Scholar 

  54. Kabashima K, Saji T, Murata T, et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002;109:883–93.

    PubMed  CAS  Google Scholar 

  55. Meinzer U, Idestrom M, Alberti C, et al. Ileal involvement is age dependent in pediatric Crohn’s disease. Inflamm Bowel Dis. 2005;11:639–44.

    Article  PubMed  Google Scholar 

  56. Aea L. Pediatric onset Crohn’s colitis is characterized by genotype-dependent age-related susceptibility. Inflamm Bowel Dis. 2007;13:1509–15.

    Article  Google Scholar 

  57. Henderson P. Genetics of childhood-onset inflammatory bowel disease. Inflamm Bowel Dis. 2010;17:346–61.

    Article  Google Scholar 

  58. Imielinski M. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009;41:1335–40.

    Article  PubMed  CAS  Google Scholar 

  59. Kugathasan S. Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat Genet. 2008;40:1211–5.

    Article  PubMed  CAS  Google Scholar 

  60. Amre D, et al. Investigation of reported associations between the 20q13 and 21q22 loci and pediatric-onset Crohn’s disease in Canadian children. Am J Gastroenterol. 2009;104:2824–48.

    Article  PubMed  CAS  Google Scholar 

  61. Pitti R, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998;396:699–703.

    Article  PubMed  CAS  Google Scholar 

  62. Hsu TL, et al. Modulation of dendritic cell differentiation and maturation by decoy receptor 3. J Immunol. 2002;168:4846–53.

    PubMed  CAS  Google Scholar 

  63. Van Limbergen J, et al. The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet. 2009;10:89–116.

    Article  PubMed  Google Scholar 

  64. Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 2008;8:458–66.

    Article  PubMed  CAS  Google Scholar 

  65. de Bakker PI, Ferreira MA, Jia X, Neale BM, Raychaudhuri S, Voight BF. Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet. 2008;17:R122–8.

    Article  PubMed  Google Scholar 

  66. Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40:955–62.

    Article  PubMed  CAS  Google Scholar 

  67. Franke A, McGovern DP, Barrett JC, et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet. 2010;42:1118–25.

    Article  PubMed  CAS  Google Scholar 

  68. Mathur AN, Chang HC, Zisoulis DG, et al. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol. 2007;178:4901–7.

    PubMed  CAS  Google Scholar 

  69. Nakazawa A, Dotan I, Brimnes J, et al. The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells. Gastroenterology. 2004;126:1347–57.

    Article  PubMed  CAS  Google Scholar 

  70. Ito T, Yang M, Wang YH, et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med. 2007;204:105–15.

    Article  PubMed  CAS  Google Scholar 

  71. Wrackmeyer U, Hansen GH, Seya T, Danielsen EM. Intelectin: a novel lipid raft-associated protein in the enterocyte brush border. Biochemistry. 2006;45:9188–97.

    Article  PubMed  CAS  Google Scholar 

  72. Lu L, Wang J, Zhang F, et al. Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells. J Immunol. 2010;184:4295–306.

    Article  PubMed  CAS  Google Scholar 

  73. Carter MJ, Di Giovine FS, Cox A, et al. The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis. Gastroenterology. 2001;121:805–11.

    Article  PubMed  CAS  Google Scholar 

  74. Carter MJ, di Giovine FS, Jones S, et al. Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians. Gut. 2001;48:461–7.

    Article  PubMed  CAS  Google Scholar 

  75. Craggs A, West S, Curtis A, et al. Absence of a genetic association between IL-1RN and IL-1B gene polymorphisms in ulcerative colitis and Crohn disease in multiple populations from northeast England. Scand J Gastroenterol. 2001;36:1173–8.

    Article  PubMed  CAS  Google Scholar 

  76. Panwala CM, Jones JC, Viney JL. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol. 1998;161:5733–44.

    PubMed  CAS  Google Scholar 

  77. Langmann T, Moehle C, Mauerer R, et al. Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes. Gastroenterology. 2004;127:26–40.

    Article  PubMed  CAS  Google Scholar 

  78. Schwab M, Schaeffeler E, Marx C, et al. Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology. 2003;124:26–33.

    Article  PubMed  CAS  Google Scholar 

  79. Borm ME, van Bodegraven AA, Mulder CJ, Kraal G, Bouma G. A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis. Int J Immunogenet. 2005;32:401–5.

    Article  PubMed  CAS  Google Scholar 

  80. Achkar JP, Dassopoulos T, Silverberg MS, et al. Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus. Am J Gastroenterol. 2006;101:572–80.

    Article  PubMed  CAS  Google Scholar 

  81. Anderson CA, Boucher G, Lees CW, et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet. 2011;43:246–52.

    Article  PubMed  CAS  Google Scholar 

  82. Steinberg MW, Turovskaya O, Shaikh RB, et al. A crucial role for HVEM and BTLA in preventing intestinal inflammation. J Exp Med. 2008;205:1463–76.

    Article  PubMed  CAS  Google Scholar 

  83. Mahida YR, Wu K, Jewell DP. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn’s disease. Gut. 1989;30:835–8.

    Article  PubMed  CAS  Google Scholar 

  84. Williams EJ, Haque S, Banks C, Johnson P, Sarsfield P, Sheron N. Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue. J Pathol. 2000;192:533–9.

    Article  PubMed  CAS  Google Scholar 

  85. Kang J, Kugathasan S, Georges M, Zhao H, Cho JH. Improved risk prediction for Crohn’s disease with a multi-locus approach. Hum Mol Genet. 2011;20:2435–42.

    Article  PubMed  CAS  Google Scholar 

  86. Wei Z, Wang K, Qu HQ, et al. From disease association to risk assessment: an optimistic view from genome-wide association studies on type 1 diabetes. PLoS Genet. 2009;5:e1000678.

    Article  PubMed  Google Scholar 

  87. Tomer G, Ceballos C, Concepcion E, Benkov KJ. NOD2/CARD15 variants are associated with lower weight at diagnosis in children with Crohn’s disease. Am J Gastroenterol. 2003;98:2479–84.

    Article  PubMed  CAS  Google Scholar 

  88. Kugathasan S, Collins N, Maresso K, et al. CARD15 gene mutations and risk for early surgery in pediatric-onset Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:1003–9.

    Article  PubMed  CAS  Google Scholar 

  89. Sun L, Roesler J, Rosen-Wolff A, et al. CARD15 genotype and phenotype analysis in 55 pediatric patients with Crohn disease from Saxony, Germany. J Pediatr Gastroenterol Nutr. 2003;37:492–7.

    Article  PubMed  CAS  Google Scholar 

  90. Wine E, Reif SS, Leshinsky-Silver E, et al. Pediatric Crohn’s disease and growth retardation: the role of genotype, phenotype, and disease severity. Pediatrics. 2004;114:1281–6.

    Article  PubMed  Google Scholar 

  91. Russell RK, Drummond HE, Nimmo EE, et al. Genotype-phenotype analysis in childhood-onset Crohn’s disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease. Inflamm Bowel Dis. 2005;11:955–64.

    Article  PubMed  Google Scholar 

  92. Roesler J, Thurigen A, Sun L, et al. Influence of CARD15 mutations on disease activity and response to therapy in 65 pediatric Crohn patients from Saxony, Germany. J Pediatr Gastroenterol Nutr. 2005;41:27–32.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We are most grateful to Dr. Judy H. Cho and Dr. Nancy McGreal who wrote the earlier version of this chapter and authorized us to use it as a template for the updated studies presented.

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Authors and Affiliations

  1. Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA

    Zhi Wei PhD

  2. Center for Applied Genomics, The Children’s Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Steven Baldassano MD, PhD Candidate & Hakon Hakonarson MD, PhD

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  1. Zhi Wei PhD
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  2. Steven Baldassano MD, PhD Candidate
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  3. Hakon Hakonarson MD, PhD
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Correspondence to Hakon Hakonarson MD, PhD .

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Editors and Affiliations

  1. Perelman School of Medicine, The Children’s Hospital of Philadelphia, University of Pennsylvania, 34th St. & Civic Ctr. Blvd., Philadelphia, 19104, Pennsylvania, USA

    Petar Mamula

  2. School of Medicine--Greenville, Pediatric Gastroenterology & Nutrition, University of South Carolina, 200 Patewood Drive, Suite A-140, Greenville, 29615, South Carolina, USA

    Jonathan E. Markowitz

  3. Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 34th St. & Civic Ctr. Blvd., Philadelphia, 19104, Pennsylvania, USA

    Robert N. Baldassano

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Wei, Z., Baldassano, S., Hakonarson, H. (2013). Genetics of Inflammatory Bowel Diseases. In: Mamula, P., Markowitz, J., Baldassano, R. (eds) Pediatric Inflammatory Bowel Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5061-0_1

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