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Pathway paradigms revealed from the genetics of inflammatory bowel disease

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  • Daniel B. Graham

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital and Harvard Medical School
    Massachusetts General Hospital and Harvard Medical School
    Center for Microbiome Informatics and Therapeutics, MIT)

  • Ramnik J. Xavier

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital and Harvard Medical School
    Massachusetts General Hospital and Harvard Medical School
    Center for Microbiome Informatics and Therapeutics, MIT)

Abstract

Inflammatory bowel disease (IBD) is a complex genetic disease that is instigated and amplified by the confluence of multiple genetic and environmental variables that perturb the immune–microbiome axis. The challenge of dissecting pathological mechanisms underlying IBD has led to the development of transformative approaches in human genetics and functional genomics. Here we describe IBD as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system. Finally, we synthesize emerging insights from multiple experimental approaches into pathway paradigms and discuss future prospects for disease-subtype classification and therapeutic intervention.

Suggested Citation

  • Daniel B. Graham & Ramnik J. Xavier, 2020. "Pathway paradigms revealed from the genetics of inflammatory bowel disease," Nature, Nature, vol. 578(7796), pages 527-539, February.
    • Handle: RePEc:nat:nature:v:578:y:2020:i:7796:d:10.1038_s41586-020-2025-2
    DOI: 10.1038/s41586-020-2025-2
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    Cited by:

    1. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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