Decanalization and the origin of complex disease
Abstract
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.
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This difference may imply different intensities of purifying selection, although other models including decanalization are also compatible with the data.
“This may imply different intensities of purifying selection, although other models, including decanalization69, are also compatible with the data.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [69]
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- Authors
- Gibson, G.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Gibson, Greg
- ORCID
- Gibson, Greg
- Venue
- Nature Reviews Genetics
- Published
- 2009-02
- Volume
- 10
- Issue
- 2
- Pages
- 134-140
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2048258507
- Cited by
- 285
- References
- 49
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 14 · 2021: 14 · 2020: 21 · 2019: 14 · 2018: 12 · 2017: 13 · 2016: 22 · 2015: 23 · 2014: 15 · 2013: 25 · 2012: 24
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- canalization, complex diseases, genetic architecture, genetic susceptibility, gene-environment interaction, cryptic genetic variation, human genome evolution, environmental disturbance
- MeSH terms
- Alleles, Mental Disorders, Diabetes Mellitus, Type 2, Environment, Humans, Immune System Diseases, Models, Genetic, Genetic Predisposition to Disease, Genetic Diseases, Inborn
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