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Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments
Open accessAbstract
The most stringent test of differential susceptibility theory is provided by randomized control trials examining the moderating role of genetic markers of differential susceptibility in experimental manipulations of the environment (Gene ×Experimental Environment interactions), being at least 10 times more powerful than correlational Gene × Environment interaction studies. We identified 22 experiments involving 3,257 participants with various developmental outcomes (e.g., externalizing problems, internalizing behaviors, and cognitive development). Effect sizes contrasting experimental versus control group were computed both for subjects with the polymorphism considered indicative of heightened susceptibility (e.g., the dopamine receptor D4 gene seven-repeat allele and the serotonin transporter polymorphic region short allele) and others expected to be low in susceptibility (e.g., the dopamine receptor D4 gene four-repeat allele and the serotonin transporter polymorphic region short allele). Clear-cut experimental support for genetic differential susceptibility emerged: the combined effect size of the interventions for the susceptible genotypes amounted to r= .33 (95% confidence interval = 0.23, 0.42;p< .01) versus a nonsignificant r= .08 (95% confidence interval = −0.02, 0.17;p= .12) for the hypothesized nonsusceptible genotypes. Macrotrials showed more evidence of genetic differential susceptibility than microtrials, and differential susceptibility was more clearly observed in trials with externalizing and cognitive outcomes than with internalizing problems. This meta-analysis shows proof of principle for genetic differential susceptibility and indicates that it is time to explore its mechanisms and limits. The concept of differential susceptibility alters the idea of constitutional “risk” factors (reactive temperament and risk genotypes), and points to intervention efficacy hidden in Gene × Environment interactions.
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There is low genetic susceptibility to positive environmental influences.
“low genetic susceptibility to (positive) environmental influences (Van IJzendoorn, & Bakermans-Kranenburg, 2015)”
From Safety First! Residential Group Climate and Antisocial Behavior: A Multilevel Meta-analysis (2025) · cites this paper as Van IJzendoorn, & Bakermans-Kranenburg, 2015
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Cites
The Ecology of Human Development: Experiments by Nature and Design
Bronfenbrenner, U. (1979) · Harvard University Press eBooks · doi:10.4159/9780674028845 · Cited by 26,084
The weirdest people in the world?
Henrich, J., Heine, S. J., & Norenzayan, A. (2010) · Behavioral and Brain Sciences · doi:10.1017/s0140525x0999152x · Cited by 12,641
The New Statistics: Why and How
Cumming, G. (2014) · Psychological Science · doi:10.1177/0956797613504966 · Cited by 3,200
Beyond diathesis stress: differential susceptibility to environmental influences
Belsky, J., & Pluess, M. (2009) · Psychological Bulletin · doi:10.1037/a0017376 · Cited by 3,039
A Nonparametric “Trim and Fill” Method of Accounting for Publication Bias in Meta-Analysis
Duval, S., & Tweedie, R. (2000) · Journal of the American Statistical Association · doi:10.1080/01621459.2000.10473905 · Cited by 2,955
Publication Bias in Meta‐Analysis: Prevention, Assessment and Adjustments
(2005) · doi:10.1002/0470870168 · Cited by 2,368
Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., Griem, A., Kovacs, M., Ott, J., & Merikangas, K. R. (2009) · JAMA · doi:10.1001/jama.2009.878 · Cited by 1,655 · cited 2×
“The first misunderstanding is the assumption that to find a replicable G E interaction, one would need a genetic main effect (e.g., Munafò Zammit, & Flint, in press; Risch et al., 2009).”
BackgroundEmpirical assessment of effect of publication bias on meta-analyses
Sutton, A. J. (2000) · BMJ · doi:10.1136/bmj.320.7249.1574 · Cited by 1,398
Epigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239
Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation
McDermott, R., Tingley, D., Cowden, J., Frazzetto, G., & Johnson, D. D. P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808376106 · Cited by 384
van IJzendoorn, M. H., Caspers, K., Bakermans-Kranenburg, M. J., Beach, S. R. H., & Philibert, R. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.008 · Cited by 264
Self-citationAndersson, E., Rück, C., Lavebratt, C., Hedman, E., Schalling, M., Lindefors, N., Eriksson, E., Carlbring, P., Andersson, G., & Furmark, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079015 · Cited by 43
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Research works printed but not linked: 59
- 10.1016/j.ajhg.2010.11.011 · DOI · Paper page
- 10.1038/sj.npp.1300054 · DOI
- 10.1037/a0030003 · DOI
- 10.1038/tp.2012.73 · DOI
- 10.1037/a0026564 · DOI
- 10.1016/j.jaac.2013.07.016 · DOI
- 10.1093/scan/nss020 · DOI
- 10.1037/a0026179 · DOI
- 10.1001/archgenpsychiatry.2009.167 · DOI · Paper page
- 10.1002/dev.20249 · DOI
- 10.1111/j.1467-8624.2012.01757.x · DOI
- 10.1017/S0954579414001308 · DOI
- Munafò, Gene × Environment interaction models: What impact should they have on clinical perceptions and practice?, Journal of Child Psychology and Psychiatry
- 10.1146/annurev-psych-010213-115100 · DOI
- 10.1017/S0954579411000071 · DOI
- 10.1016/j.biopsych.2013.09.006 · DOI
- 10.1111/j.1751-228X.2011.01112.x · DOI
- 10.1017/S0954579410000611 · DOI · Paper page
- 10.1375/twin.2.2.62 · DOI
- Cohen, 1988, Statistical power analysis for the behavioral sciences
- 10.1017/S0954579414001278 · DOI
- 10.1017/S095457941400128X · DOI
- 10.1111/jcpp.12042 · DOI
- 10.1017/S0954579414001266 · DOI
- Borenstein, 2005, Comprehensive meta-analysis: A computer program for research synthesis
- 10.1038/mp.2012.92 · DOI
- 10.1111/jcpp.12075 · DOI
- 10.1038/mp.2009.44 · DOI · Paper page
- 10.1111/j.1467-8721.2007.00525.x · DOI · Paper page
- 10.1037/a0020835 · DOI
- Mullen, 1989, Advanced BASIC meta-analysis
- 10.1017/S0954579412000065 · DOI
- 10.1146/annurev-psych-010814-015407 · DOI
- 10.1037/a0031253 · DOI
- 10.1017/S095457941300059X · DOI
- 10.1111/j.1601-183X.2012.00868.x · DOI
- 10.1016/j.biopsych.2011.07.004 · DOI
- 10.1017/S095457941400131X · DOI
- 10.1017/S0954579414001291 · DOI
- 10.1017/S0954579411000113 · DOI
- 10.1037/a0030196 · DOI
- 10.1037/0022-006X.74.2.356 · DOI
- 10.1038/nrg2764-c1 · DOI
- 10.1002/dev.20152 · DOI · Paper page
- 10.1016/j.biopsych.2010.07.021 · DOI · Paper page
- 10.1111/j.0006-341X.2000.00455.x · DOI · Paper page
- 10.1002/9780470743386 · DOI · Paper page
- 10.1002/ajmg.b.32054 · DOI
- 10.1093/scan/nsr089 · DOI
- Robbins, 1999, Fundamental neuroscience, 1246
- 10.1017/S0954579414001345 · DOI
- 10.1192/bjp.bp.110.085225 · DOI
- 10.1017/S0954579410000635 · DOI
- 10.1038/sj.mp.4001950 · DOI
- 10.1161/STROKEAHA.110.611434 · DOI
- 10.1037/0012-1649.44.1.293 · DOI · Paper page
- 10.1034/j.1600-0447.2000.102004241.x · DOI
- 10.1016/j.biopsycho.2005.02.001 · DOI
- 10.1037/0033-2909.114.2.376 · DOI · Paper page
Cited by
Sorted by citations
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Keers, R., Coleman, J. R. I., Lester, K. J., Roberts, S., Breen, G., Thastum, M., Bögels, S., Schneider, S., Heiervang, E., Meiser-Stedman, R., et al. (2016) · Psychotherapy and Psychosomatics · doi:10.1159/000444023 · Cited by 127
Hygen, B. W., Belsky, J., Stenseng, F., Lydersen, S., Guzey, I. C., & Wichstrøm, L. (2015) · Developmental Psychology · doi:10.1037/dev0000020 · Cited by 48
Parenting Interacts With Plasticity Genes in Predicting Behavioral Outcomes in Preschoolers
Letourneau, N. L., de Koning, A. P. J., Sekhon, B., Ntanda, H. N., Kobor, M., Deane, A. J., Morin, A. M., Dewey, D., Campbell, T. S., Giesbrecht, G. F., et al. (2020) · Canadian Journal of Nursing Research · doi:10.1177/0844562119863612 · Cited by 12
Safety First! Residential Group Climate and Antisocial Behavior: A Multilevel Meta-analysis
E. M. A, E., J. J, R., G. H. P, V. D. H., E. J. E, H., C. H. Z, K., K. S, N., S, V., J. D, L., G. J. J. M, S., E, K., et al. (2025) · International Journal of Offender Therapy and Comparative Criminology · doi:10.1177/0306624x241252052 · Cited by 4
Metadata
- Authors
- van Ijzendoorn, M. H., & Bakermans-Kranenburg, M. J.
- Affiliations
- Leiden University (NL)
- Corresponding author
- van Ijzendoorn, Marinus H.
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-02
- Volume
- 27
- Issue
- 1
- Pages
- 151-162
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- OpenAlex
- W2111754442
- Cited by
- 146
- References
- 12
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 18 · 2021: 9 · 2020: 12 · 2019: 15 · 2018: 10 · 2017: 19 · 2016: 25 · 2015: 16
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- differential susceptibility theory, gene-environment interaction, genetic moderators, externalizing problems, internalizing problems, cognitive development, intervention efficacy
- MeSH terms
- Humans, Research Design, Randomized Controlled Trials as Topic, Genetic Predisposition to Disease, Gene-Environment Interaction
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