Open AccessNetwork Modeling of Crohn’s Disease Incidence
Author(s) -
Jean–Marc Victor,
Gaëlle Debret,
Annick Lesne,
Leigh Pascoe,
Pascal Carrivain,
Gilles Wainrib,
JeanPierre Hugot
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0156138
Subject(s) - disease , ankylosing spondylitis , incidence (geometry) , crohn's disease , medicine , allele , odds ratio , epidemiology , genetics , bioinformatics , biology , immunology , gene , pathology , physics , optics
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.