The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents’ own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children’s externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent–child communication, less parent–child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children’s environmental experiences, and the role of children’s genotypes in shaping parent–child relationships.

Gene-environment correlations and interactions for the relationship between emotional problems (EP) and family environment in adolescents in low- to middle-income countries (LMIC) have been rarely investigated. In total, 3207 adolescent twins aged 12–18 (Mean = 14.6 ± 1.73) years attending public schools in Lagos State in Nigeria completed measures of EP and Family Chaos (FC). Model-fitting analyses suggested that genetic and non-shared environmental influences on EP were 21% and 71%, respectively, and the corresponding estimates were 23% and 71% for FC. Shared environmental influences were not significant (8% and 6% respectively). Phenotypic correlation between EP and FC was .30 (95% CI = .27–.34), which was significantly influenced by genetic (A – 49%, 95% CI: 0.01–0.97) and non-shared environmental factors (E – 32%, 95% CI: 0.10–0.54). Shared environmental influences were not significant (C – 19%, 95% CI: −0.13 to 0.50). Moderation effects were significant whereby as FC increased, A on EP decreased (βA = −0.07, 95% CI: −0.12 to −0.02) while E increased (βE = 0.06, 95% CI: 0.03–0.09). Our findings indicate that genetic and non-shared environmental risk factors may mediate the relationship between EP and FC, and that as FC increases, protective genetic influences on EP may be attenuated, whereas environmental influences may become stronger in adolescents in LMIC.

Past research demonstrates a phenotypic relationship between childhood maltreatment and adult health problems. Explanations of this association usually point to either: (a) a direct causal link, whereby exposure to early stress disrupts biological functioning during sensitive periods of development; or (b) an indirect effect operating through socioeconomic attainment, poor health behaviors, or some other pathway leading from childhood to adulthood. The current study examined whether the association between childhood maltreatment and adult health reflects genetic or environmental mediation. Using a large sample of adult American twins, we separately estimated univariate biometric models of child maltreatment and adult physical health, followed by a bivariate biometric model to estimate genetic and environmental correlations between the two variables. We found that a summary count of chronic health conditions shared non-trivial genetic overlap with childhood maltreatment. Our results have implications for understanding the relationship between maltreatment and health as one of active interplay rather than a simple cause and effect model that views maltreatment as an exogenous shock.

Aims – Genetics can offer new resources to epidemiology. This review will consider recent findings regarding the link between stress and depression as an example to illustrate the added value of employing genetics in epidemiological studies. Methods – Systematic review of medical and psychological databases. Results – Genetic and environmental factors may correlate. This suggests the potential for genetic mediation of the exposure to the environment. Gene-environment correlations can help epidemiologists to better understand causal pathways and suggest effective therapeutic strategies. Genetic and environmental factors may also interact. This suggests the potential for genetic modification of environmental effects on disease risk. Gene-environment interactions can help epidemiologists to identify vulnerable individuals and strata-specific environmental effects. Conclusions – New models of disease based on the interplay between genes and environments are providing epidemiology with a new set of testable hypotheses that will advance our understanding of mental health and illness.

Declaration of Interest: Dr. Danese is holder of the Wellcome Trust Research Training Fellowship in Clinical Science.