Genotype × Environment Interaction in Psychopathology: Fact or Artifact?
Open accessAbstract
Recent studies have claimed to detect interaction between candidate genes and specific environmental factors (Genotype × Environment interaction, G × E) in susceptibility to psychiatric disorder. The objective of the present study was to examine possible artifacts that could explain widely publicized findings. The additive effects of candidate genes and measured environment on liability to disorder were simulated under a model that allowed for mixture of distributions in liability conditional on genotype and environment. Simulated liabilities were dichotomized at a threshold value to reflect diagnosis of disorder. Multiple blocks of simulated data were analyzed by standard statistical methods to test for the main effects and interactions of genes and environment on outcome. The main outcome of this study was simulated liabilities and diagnoses of major depression and antisocial behavior. Analysis of the dichotomized data by logistic regression frequently detected significant G × E interaction even though none was present for liability. There is therefore reason to question the biological significance of published findings.
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Logistic regression techniques used to identify interactions in gene-environment studies can produce both false-positive and false-negative findings.
“The use of logistic regression techniques to identify interactions in GxE studies is widespread, but it is important to note that this technique can lead to both false-positive and false-negative findings”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Eaves 2006
Psychiatric disorders tend to co-occur and are heterogeneous, so efforts to examine dichotomous diagnoses are problematic.
“Psychiatric disorders tend to co-occur, and are also heterogeneous, so that efforts to examine dichotomous diagnoses, a common approach in genetic research, are problematic (Eaves 2006).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Eaves 2006
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“For example, Eaves’ (2006) simulation of GxE interactions in depression and antisocial behavior suggested that dichotomization (i.e., using a “clinical cutoff” to assign a yes/no diagnosis) and sampling from the extremes of a distribution can significantly inflate the likelihood of potential…”
BackgroundMethodMeasured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder
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MAOA‐uVNTR and early physical discipline interact to influence delinquent behavior
Edwards, A. C., Dodge, K. A., Latendresse, S. J., Lansford, J. E., Bates, J. E., Pettit, G. S., Budde, J. P., Goate, A. M., & Dick, D. M. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02196.x · Cited by 67 · see citing works
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- Authors
- Eaves, L. J.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Eaves, Lindon J.
- Venue
- Twin Research and Human Genetics
- Publisher
- Cambridge University Press (CUP)
- Published
- 2006-02-01
- Volume
- 9
- Issue
- 1
- Pages
- 1-8
- ISSN
- 1832-4274 (ISSN-L)
- 1839-2628
- OpenAlex
- W2105719520
- Cited by
- 183
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 11 · 2014: 7 · 2013: 13 · 2012: 13
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Twin Research and Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH068521, R29MH055557, MH45268, MH68521, R01MH045268, MH-55557)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- gene-environment interaction, candidate genes, major depressive disorder, antisocial behavior, simulation study, measurement error, logistic regression
- MeSH terms
- Mental Disorders, Disease Susceptibility, Environmental Exposure, Epidemiologic Methods, Genotype, Humans, Phenotype, Regression Analysis, Research Design, Models, Statistical, Artifacts, Quantitative Trait, Heritable, Genetic Predisposition to Disease
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