Network Modeling of Crohn's Disease Incidence.
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.


RESULTS
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.


CONCLUSIONS
Modeling disease incidence may help to understand disease causative chains, to delineate the potential of personalized medicine, and to monitor epidemiological changes in CGD.
Laboratoire 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.|Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR 5535, Université de Montpellier, Montpellier, France.
Jean-Marc
JM
Victor
Laboratoire 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.
Gaëlle
G
Debret
Laboratoire 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.|Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR 5535, Université de Montpellier, Montpellier, France.
Annick
A
Lesne
Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain, Paris, France.
Leigh
L
Pascoe
Laboratoire 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.
Pascal
P
Carrivain
Ecole Normale Supérieure, Paris, France.|Labex inflamex, Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.
Gilles
G
Wainrib
Labex inflamex, Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.|UMR 1149, Institut National de la Santé et de la Recherche Médicale, Paris, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.
Jean-Pierre
http://orcid.org/0000-0002-8446-6056
JP
Hugot
D000328:Adult; D000483:Alleles; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004843:Epistasis, Genetic; D005260:Female; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D006801:Humans; D015994:Incidence; D008297:Male; D008390:Markov Chains; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology