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Genetics of Inflammatory Bowel Diseases

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Pediatric Inflammatory Bowel Disease

Abstract

The inflammatory bowel diseases, Crohn disease and ulcerative colitis, are caused by the immune system’s dysregulated response to the gut flora and environmental exposures in genetically susceptible individuals. The last 20 years have shown great progress in understanding the basis of this genetic susceptibility. The first efforts involved genetic epidemiology and family studies to show unequivocally the hereditary contribution to IBD. Later, studies utilizing sib pair linkage analysis revealed one of the first replicable associations in IBD, indeed in complex mode of inheritance diseases generally, the NOD2 polymorphisms. In 2006, the introduction of genome-wide association studies brought a new model for identifying genomic loci conferring more modest risk of IBD. Through the aggregation of many such GWAS data sets in meta-analysis, at least 200 loci have been identified that underlie the genetic susceptibility. Next-generation sequencing (NGS) studies are showing promise in specific pediatric populations with IBD or its genetic mimics. In this chapter, we will review some genetic epidemiology, specific genes identified, new approaches to identifying loci using sequencing, and genotype-phenotype correlations.

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Acknowledgment

We are most grateful to Dr. Judy H. Cho, Dr. Nancy McGreal, Dr. Zhi Wei, and Steve Baldassano (MD/PhD student) who wrote earlier versions of this chapter.

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Authors and Affiliations

  1. Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Christopher J. Cardinale MD, PhD

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

    Hakon Hakonarson MD, PhD

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  1. Christopher J. Cardinale MD, PhD
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Correspondence to Christopher J. Cardinale MD, PhD .

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Editors and Affiliations

  1. Division of GI, Hepatology & Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Petar Mamula

  2. Division of GI, Hepatology & Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Andrew B. Grossman

  3. Division of GI, Hepatology & Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Robert N. Baldassano

  4. Division of GI, Hepatology & Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Judith R. Kelsen

  5. Division of Pediatric Gastroenterology & Nutrition, University of South Carolina School of Medicine - Greenville, Greenville, South Carolina, USA

    Jonathan E. Markowitz

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Cardinale, C.J., Hakonarson, H. (2017). Genetics of Inflammatory Bowel Diseases. In: Mamula, P., Grossman, A., Baldassano, R., Kelsen, J., Markowitz, J. (eds) Pediatric Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-49215-5_1

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