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.
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This work is supported by grants from the Helmsley Charitable Trust and NIH (to R.J.X.). We thank H. Kang for valuable scientific input, editorial assistance and illustrative design.
The authors declare no competing interests.
Peer review information Nature thanks Jeff Barrett and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Graham, D.B., Xavier, R.J. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 578, 527–539 (2020). https://doi.org/10.1038/s41586-020-2025-2
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