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Genetics of Inflammatory Bowel Diseases

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Pediatric Inflammatory Bowel Disease

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Abstract

The inflammatory bowel diseases, Crohn disease and ulcerative colitis, are caused by the immune system’s dysregulated response to 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 epidemiology and family studies to assess 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 (GWAS) brought a new model for identifying genomic loci conferring a more modest risk of IBD. Through the aggregation of several GWAS datasets in meta-analysis, at least 240 loci have been identified. Next-generation sequencing (NGS) technology was introduced in the last decade and successfully identified multiple new risk variants, in previously identified GWAS genes. Sequencing has also been successful in identifying monogenic defects in very-early-onset (VEO) IBD cases as well as in some other 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, and genotype-phenotype correlations.

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Acknowledgement

We thank Drs. Judy H. Cho, Nancy McGreal, Zhi Wei, and Steve Baldassano, who helped with writing of 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 & Hakon Hakonarson

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Hakon Hakonarson

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  1. Christopher J. Cardinale
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Correspondence to Hakon Hakonarson .

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Editors and Affiliations

  1. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Petar Mamula

  2. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Judith R. Kelsen

  3. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Andrew B. Grossman

  4. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Robert N. Baldassano

  5. Division of Pediatric Gastroenterology, Prisma Health Children’s Hospital—Upstate, Greenville, SC, USA

    Jonathan E. Markowitz

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Cardinale, C.J., Hakonarson, H. (2023). Genetics of Inflammatory Bowel Diseases. In: Mamula, P., Kelsen, J.R., Grossman, A.B., Baldassano, R.N., Markowitz, J.E. (eds) Pediatric Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-031-14744-9_1

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