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Network Modeling of Crohn's Disease Incidence
Jean-Marc Victor1,2, Gaëlle Debret1, Annick Lesne1,2
1Laboratoire de Physique Théorique de la Matière Condensée, UMR 7600 Centre National de la Recherche Scientifique & Université Pierre et Marie Curie-Paris 6, Sorbonne Universités, Paris, France.
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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