Interactions Between Genes & the Environment
Written by Gail S. Anderson   

GENES DO NOT ACT ALONE and neither does the environment. Genes and the environment frequently act together. They may correlate with each other or interact. These two relationships are quite different and must be distinguished in order to understand their mechanisms.

Gene–environment correlations
Gene–environment correlations can be mistaken for gene × environment interactions and must be separated. It has been hypothesized that there are three forms of gene–environment correlations.1,3,4

1. Passive gene–environment correlations

The first is referred to as passive and occurs when a child’s genetic background and environment come from one source — that of the parents. For example, adolescents may exhibit aggressive behavior as a result of both inheriting genes that predispose them to aggression and growing up in an environment in which their parents exhibit aggression, making the two factors difficult to separate.1

2. Reactive gene–environment correlations

The second is reactive, in which genetically influenced behavior induces a certain type of environment. For example, a genetic predisposition to shyness may make an adolescent less responsive to peer overtures, resulting in isolation that leads to further inhibition, again making it difficult to disentangle the environmental and genetic components of the behavior.1

3. Active gene–environment correlations

Active correlation is hypothesized to occur when adolescents pick their environments based on their genetic predispositions.1 For example, an adolescent who is predisposed to antisocial behavior may seek out peers who are like-minded with whom to engage in criminal acts.

In all cases, it is hard to tease apart the genetic and environmental influences.

Gene × environment interactions
We now understand that people with different genotypes respond differently to the same environment. In other words, 2 or 20 people may be exposed to the same environment, and all may react differently. For example, we know there are multitudes of risk factors for criminal behavior (such as severe child abuse), but many people — in fact, the majority — who are exposed to this risk factor will not commit a crime. Sociological theories do not explain why the same environment can produce such disparate results, but biosocial criminology can show that one explanation for the disparity is the closely interwoven relationships between genetic and environmental factors.5

Frequently, there is an interaction between a person’s genetic makeup and the environment experienced. This occurs when an individual’s particular genotype is sensitive or vulnerable to environmental factors; individuals with different genotypes will react differently to different environmental triggers.1 In other words, the effect the environment will have on an individual’s behavior depends on genetic makeup, and the effect an individual’s genetic makeup will have on behavior depends on the environment experienced.6 This is referred to as gene × environment interactions, or G × E interactions. It is this interaction that explains why some people who experience terribly adverse environments never commit crimes and why some others who experience a nurturing environment do commit crimes. If an individual does not have a genetic predisposition toward criminal behavior, that person may never commit a crime, even when faced with environmental adversity. If an individual does have a genetic predisposition for criminal behavior but does not experience a triggering environment, then that person too may never exhibit criminal behavior. It is only when an individual has both a genetic predisposition and experiences an adverse or triggering environment that the risk for criminal behavior is high.6 However, although the existence of both increases risk, it still does not guarantee a criminal outcome. Moreover, both genetic and environmental risk factors act in gradients, with both increasing and ameliorating risk, and there are many individual and interacting effects within both genetic and environmental influences, all of which serve to moderate or amplify behavior. Although the focus of most biosocial studies is to determine the etiology of behavior and identifying risk factors, such studies also identify protective factors. In particular, understanding G × E interactions allows us to recognize protective environments that will prevent a risky genotype from being expressed and so can inform intervention and prevention strategies.6

An example of G × E interactions
There are a multitude of examples of G × E interactions that are now being studied. One example is seen in the development of schizophrenia and bipolar disorder. Numerous studies have shown both environmental and genetic causes for these psychiatric disorders, and a large number of genes have been implicated, with each contributing only a small level of susceptibility.2

More recently a G × E interaction has been proposed, and a large number of studies have looked at genetic interactions with a range of environmental factors. In a review of such studies, the majority considered variation in genes that code for catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein (FKBP5).2 COMT is an enzyme that breaks down a number of substances in the body, such as some neurotransmitters and certain drugs, and is implicated in several psychiatric disorders.7 BDNF is involved in growth and survival of brain neurons.8 FKBP5 is a binding protein that regulates steroid receptors, and methylation of the gene is thought to moderate the effects of genetic and environmental risk factors for psychiatric diseases.9 Most of these studies found significant interactions between certain alleles of these genes and cannabis use, as well as early-life stress or childhood trauma, which increased risk for schizophrenia and bipolar disorder, although there were far fewer studies on bipolar disorder. A few studies also found some interactions between the alleles and infectious diseases, birth complications, and season of birth.2

G × E interaction models
In attempting to understand the underlying mechanisms of the complex G × E interactions that underlie the expression of criminal or antisocial behavior, a number of hypotheses, or models, have been developed, based on the proposed different methods in which genetic polymorphic risk factors increase or decrease susceptibility to unfavorable environments.6

1. Diathesis stress model

The diathesis stress model assumes that a genotype (involving many polymorphisms or different risk alleles) confers risk and will lead to an extremely adverse outcome if the individual is exposed to a negative environment. However, in a good environment the outcome will not be as negative or may not occur at all.10 This model stresses the adverse environment and its effects on a risky genotype that is vulnerable to environmental triggers, resulting in antisocial behavior.6 This model, therefore, states that the fundamental causes of antisocial behavior are environmental triggers.11

For example, several studies have shown that genetic risk factors for antisocial behavior are potentiated in the presence of parental conflict. In a study of over 1,300 twin pairs aged 17 years, genetic risk for externalizing behaviors was greatly exacerbated by increased environmental adversity and parental negativity,12 and similarly, in a study of 720 families genetic risk factors for antisocial behavior had much greater influence when parents were negative or less affectionate.13 This is perhaps the most common model used to explain G × E interactions. The social control model is very similar to the diathesis stress model but highlights the presence or absence of social resources rather than an adverse environment as the trigger.11 For example, high cigarette taxation has been found to reduce the genetic influence on developing a smoking habit, which is considered to be a form of social control.11

2. Bioecological model

The bioecological model states that genetic effects are only expressed in a positive environment and are restricted and not expressed in a negative environment.10 In other words, this model suggests that, in some situations, genetic risk factors may reach their highest dominance in the absence of an adverse environment.14 An example of the bioecological model is parent-child conflict, in contrast to parent-adolescent conflict, which is believed to fit the diathesis stress model. In a U.S. study of 500 pairs of twins, shared environment was many times more influential on antisocial behavior in children with high levels of parental conflict than in those with low levels of conflict, but conversely, genetic factors were much more significant in the development of antisocial behavior in children with low levels of parental conflict.14

3. Differential susceptibility

Differential susceptibility suggests that certain genes or polymorphic genotypes do not simply confer risk, but instead represent a type of gene plasticity or a level of malleability to the environment, which may have negative or positive outcomes.10,15(p885) In other words, a child with a risky genotype who is exposed to a negative environment will have a very high risk for a bad outcome, but if that same child with a risky genotype was placed in a more positive environment, the child may have an even more positive outcome than a child without the risky genotype.1

This model focuses less on the adverse environment and looks more at an individual’s susceptibility to the effects of environment. For example, certain genes involved in neurotransmitter production and function (DRD4 and 5HTTLPR, which we will explore in Chapter 9) are considered to be plasticity alleles.11(p716) Studies have shown that individuals who possess certain alleles of these genes (the 7R allele in DRD4 and the shorter allele in 5HTTLPR) are not only significantly more likely to be aggressive when exposed to extremely adverse environmental conditions but also significantly less likely to be aggressive in extremely favorable environments.16

In a study of carriers of the risk allele for another dopaminergic gene, DRD2, adolescents who were homozygous for this allele were much more likely than those who were heterozygous or homozygous for a non-risk allele to exhibit very seriously antisocial behavior if they were raised in a family that was not close, but they were substantially less likely to exhibit such behavior when raised in a close family, which supports differential susceptibility.11

This model is important because it suggests that we should not just focus on adverse or non-adverse environments but also consider the entire range of environments, as it indicates that normal or usual environments would not provoke any antisocial response even in those with risky genotypes.11 Belsky argued that risk alleles should instead be considered plasticity alleles and that individuals with higher numbers of plasticity alleles are more likely to be impacted, either positively or negatively, by an environment than individuals with lower numbers of plasticity alleles. Therefore, G × E interactions, in this model, are the result of the same environment having a different effect on people, depending on the number of plasticity genes they possess.15,17

4. Social distinction model

A less referenced model is the social distinction model, which is quite different because it does not suggest that the environment triggers a genotype to act in a certain way. Genetic factors are only identifiable in the most favorable environments.11 For example, in a study on the relationship between the e4 allele of the apolipoprotein, or APOE, gene (which increases the risk of developing Alzheimer’s disease) and cognitive functioning in elderly people, the allele appeared to be risky for individuals living in organized, well-kept environments but less risky for those living in social disorder.18 The authors of this study referred to this as non-causal G × E interaction.

5. Social push model

The social push model focuses on the differences between normal and abnormal social environments, rather than adverse environments, and suggests that genetic factors are relevant in normal environments, but in extreme environments, the social environment “pushes” the phenotype, so the genotype has less relevance.11 For example, heritability of body mass index is highest in adolescents enrolled in schools with normal body size expectations, but heritability is lower in schools in which body mass index extremes are normal, as the environment is driving the trait and the genotype cannot differentiate between individuals.11

Interventions considering G × E interactions
When considering intervention strategies, it is very important to consider G × E interactions; most intervention strategies fail to recognize that individuals with particular genetic risks may respond better to changes in environmental risks.6 This can also confound studies, as individuals with certain genotypes may be more likely to participate in an experimental intervention treatment, thus biasing the results, which would not indicate the efficacy for individuals with a different genotype. Therefore, in order to truly understand the genetic and environmental influences, randomized experiments are required in which participants are not allowed to self-select.

For example, a study of 440 African American families in Georgia assessed the efficacy of family-centered interventions on behaviors such as delinquency, substance abuse, and unsafe sexual practices in relation to the families’ genetic makeup.19 The genotype that the authors considered involved the transporter gene for the neurotransmitter serotonin, which we will consider in detail in Chapter 9. A particular allele for this gene, referred to as the shorter allele, has been shown to increase risky behavior, so the authors used a randomized experiment to determine whether youth who had the shorter allele would be more or less likely to exhibit risky behavior if they participated in the intervention program. The results showed that risky behavior was higher in youth with the shorter allele and that youth who had the at-risk genotype and did not participate in the intervention program were twice as likely to exhibit risky behavior in comparison with at-risk youth who did participate or youth not at risk.19 A significant interaction was seen between the genotype and treatment.19

In a follow-up study, the researchers looked at older adolescents in the same intervention program to see whether another neurotransmitter gene, the dopamine D4 receptor gene, regulated the effect of the program on substance abuse.20 The results showed that genetic risk increased substance abuse, but when broken down by sex, the relationship held true only in males. There was also a G x E interaction for males only,20 supporting the differential susceptibility model, as high-risk youth were found to be particularly susceptible to risk, both genetically and environmentally, but at the same time were also more susceptible to prosocial protective environments such as those provided by the intervention program.6

Understanding G × E interactions will help us better identify the most important environmental factors that influence antisocial behavior and so will inform future intervention strategies. Genetically informed studies can identify personality and risk factors that are particularly amenable to intervention and result in behavioral changes.6 These studies also show the types of individuals that are most likely to benefit from intervention and at which developmental stage treatment should be aimed.6

About the Author
Gail S. Anderson earned a BSc (Honors) in zoology from Manchester University, England, and a Masters of Pest Management and PhD in medical and veterinary entomology from Simon Fraser University. Her specialty is forensic entomology, the use of insects in death investigations. Anderson is one of only three board-certified forensic entomologists in Canada. She is a Professor in the School of Criminology at Simon Fraser University, Burnaby, British Columbia, Canada, holds a Burnaby Mountain Endowed Professorship, and is also undergraduate director and co-director of the Centre for Forensic Research and a forensic consultant to the Royal Canadian Mounted Police (RCMP) and municipal police across Canada. Her work has been featured on many television programs on networks including Discovery Channel, Planet Education, History Channel, Knowledge Network, and CBC. She was a recipient of Canada’s “Top 40 under 40 Award” in 1999, a YWCA Women of Distinction Award for Science and Technology in 1999, and the Simon Fraser University Alumni Association Outstanding Alumni Award for Academic Achievement in 1995. She was listed in Time magazine as one of the top five innovators in the world, this century, in the field of Criminal Justice in 2001 and received the Derome Award from the Canadian Society of Forensic Sciences. In 2014, she received the Dean’s Medal for Academic Excellence, and, in 2015, she was listed as one of the six most influential scientists in British Columbia. In 2017, she received the American Academy of Forensic Sciences Pathology and Biology Section Award for Achievement in the Life Sciences.

1. Mullineaux, P.Y. and DiLalla, L.F. 2015. Genetic influences on peer and family relationships across adolescent development: Introduction to the special issue. J. Youth Adolesc. 44(7): 1347–1359.

2. Misiak, B., Stramecki, F., Gaweda, L., et al. 2018. Interactions between variation in candidate genes and environmental factors in the etiology of schizophrenia and bipolar disorder: A systematic review. Mol. Neurobiol. 55(6): 5075–5100.

3. Plomin, R., McClearn, G.E., Pedersen, N.L., Nesselroade, J.R., and Bergeman, C.S. 1988. Genetic influence on childhood family environment perceived retrospectively from the last half of the life span. Develop. Psychol. 24(5): 738–745.

4. Scarr, S. and McCartney, K. 1983. How people make their own environments: A theory of genotype-environment effects. Child Develop. 54: 424–435.

5. Beaver, K.M., Mancini, C., DeLisi, M., and Vaughn, M.G. 2011. Resiliency to victimization: The role of genetic factors. J. Interpers. Violence 26(5): 874–898.

6. Gajos, J.M., Fagan, A.A., and Beaver, K.M. 2016. Use of genetically informed evidence-based prevention science to understand and prevent crime and related behavioral disorders. Crim. Public Pol. 15(3): 683–701.

7. Mill, J., Dempster, E., Caspi, A., Williams, B., Moffitt, T., and Craig, I. 2006. Evidence for monozygotic twin (MZ) discordance in methylation level at two CpG sites in the promoter region of the catechol-O-methyltransferase (COMT) gene. Am. J. Med. Genet. Part B. Neuropsychiatric Genet. 141B(4): 421–425.

8. Acheson, A., Conover, J.C., Fandl, J.P., et al. 1995. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 374(6521): 450–453.

9. Weder, N., Zhang, H., Jensen, K., et al. 2014. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J. Am. Acad. Child Adolesc. Psychiatry 53(4): 417–424 e5.

10. Bersted, K.A. and DiLalla, L.F. 2016. The influence of DRD4 genotype and perinatal complications on preschoolers’ negative emotionality. J. Appl. Developmental Psychol. 42: 71–79.

11. Boardman, J.D., Menard, S., Roettger, M.E., Knight, K.E., Boutwell, B.B., and Smolen, A. 2014. Genes in the dopaminergic system and delinquent behaviors across the life course: The role of social controls and risks. Crim. Justice Behav. 41(6): 713–731.

12. Hicks, B.M., South, S.C., DiRago, A.C., Iacono, W.G., and McGue, M. 2009. Environmental adversity and increasing genetic risk for externalizing disorders. Arch. Gen. Psychiatry 66(6): 640–648.

13. Feinberg, M.E., Button, T.M.M., Neiderhiser, J.M., Reiss, D., and Hetherington, E.M. 2007. Parenting and adolescent antisocial behavior and depression. Arch. Gen. Psychiatry 4(64): 4.

14. Burt, S.A. and Klump, K.L. 2014. Parent-child conflict as an etiological moderator of childhood conduct problems: An example of a “bioecological” gene-environment interaction. Psychol. Med. 44(5): 1065–1076. References 127

15. Belsky, J. and Pluess, M. 2009. Beyond diathesis stress: Differential susceptibility to environmental influences. Psychol. Bull. 135(6): 885–908.

16. Simons, R.L., Lei, M.K., Beach, S.R., Brody, G.H., Philibert, R.A., and Gibbons, F.X. 2011. Social environmental variation, plasticity genes, and aggression: Evidence for the differential susceptibility hypothesis. Am. Sociol. Rev. 76(6): 833–912.

17. Beaver, K., Nedelec, J.L., Schwartz, J.A., and Connolly, E.J. 2014. Evolutionary behavioral genetics of violent crime, In: The Evolution of Violence, Shackelford, T.K. and Hansen, R.D., editors. New York: Springer; pp. 117–136.

18. Boardman, J.D., Barnes, L.L., Wilson, R.S., Evans, D.A., and Mendes de Leon, C.F. 2012. Social disorder, APOE-E4 genotype, and change in cognitive function among older adults living in Chicago. Soc. Sci. Med. 74(10): 1584–1590.

19. Brody, G.H., Beach, S.R.H., Philibert, R.A., Chen, Y.-F., and Murry, V.M. 2009. Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene environment hypotheses tested via a randomized prevention design. Child Develop. 80(3): 645–661.

20. Brody, G.H., Chen, Y.F., Beach, S.R., et al. 2014. Differential sensitivity to prevention programming: A dopaminergic polymorphism-enhanced prevention effect on protective parenting and adolescent substance use. Health Psychol. 33(2): 182–191.

This article appeared in the January-February 2020 issue of Evidence Technology Magazine.
You can view that issue here.

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