Decanalization and the origin of complex disease

Nat Rev Genet. 2009 Feb;10(2):134-40. doi: 10.1038/nrg2502. Epub 2009 Jan 2.


Complex genetic disease is caused by the interaction between genetic and environmental variables and is the predominant cause of mortality globally. Recognition that susceptibility arises through the combination of multiple genetic pathways that influence liability factors in a nonlinear manner suggests that a process of 'decanalization' contributes to the epidemic nature of common genetic diseases. The rapid evolution of the human genome combined with marked environmental and cultural perturbation in the past two generations might lead to the uncovering of cryptic genetic variation that is a major source of disease susceptibility.

Publication types

  • Review

MeSH terms

  • Alleles*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Environment*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Immune System Diseases / genetics
  • Mental Disorders / genetics
  • Models, Genetic*