Network Modeling of Crohn's Disease Incidence

J. M. Victor (1) , G. Debret (1) , A. Lesne (1) , L. Pascoe (2) , P. Carrivain (3) , G. Wainrib (4, 5) , J. P. Hugot (6)

1 LPTMC - Laboratoire de Physique Théorique de la Matière Condensée
2 CEPH - Centre d'Etude du Polymorphisme Humain
3 IGH - Institut de génétique humaine
4 ENS-PSL - École normale supérieure - Paris
5 USPC - Université Sorbonne Paris Cité
6 OSEB - Origine, structure et évolution de la biodiversité

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.

Domaines: Hépatologie et Gastroentérologie; Biochimie, Biologie Moléculaire; Santé

J. M. Victor, G. Debret, A. Lesne, L. Pascoe, P. Carrivain, et al.. Network Modeling of Crohn's Disease Incidence. PLoS ONE, 2016, 11 (6), pp.e0156138. ⟨10.1371/journal.pone.0156138⟩. ⟨hal-02187347⟩