Network Modeling of Crohn’s Disease Incidence

Victor, J. M.; Debret, G.; Lesne, A.; Pascoe, L.; Carrivain, P.; Wainrib, G.; Hugot, J. P.

PLoS One

2016 / vol 11 / pages e0156138


BACKGROUND: Numerous genetic and environmental risk factors play a role in human complex genetic disorders (CGD). However, their complex interplay remains to be modelled and explained in terms of disease mechanisms. METHODS AND FINDINGS: Crohn’s Disease (CD) was modeled as a modular network of patho-physiological functions, each summarizing multiple gene-gene and gene-environment interactions. The disease resulted from one or few specific combinations of module functional states. Network aging dynamics was able to reproduce age-specific CD incidence curves as well as their variations over the past century in Western countries. Within the model, we translated the odds ratios (OR) associated to at-risk alleles in terms of disease propensities of the functional modules. Finally, the model was successfully applied to other CGD including ulcerative colitis, ankylosing spondylitis, multiple sclerosis and schizophrenia. CONCLUSION: Modeling disease incidence may help to understand disease causative chains, to delineate the potential of personalized medicine, and to monitor epidemiological changes in CGD.

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1932-6203 (Electronic) 1932-6203 (Linking)

PMCID: PMC4911211

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