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Original Investigation |

Genetic and Environmental Influences on the Familial Transmission of Externalizing Disorders in Adoptive and Twin Offspring

Brian M. Hicks, PhD1; Katherine T. Foster, BA1,2; William G. Iacono, PhD3; Matt McGue, PhD3
[+] Author Affiliations
1Department of Psychiatry, University of Michigan, Ann Arbor
2Department of Psychology, University of Michigan, Ann Arbor
3Department of Psychology, University of Minnesota, Minneapolis
JAMA Psychiatry. 2013;70(10):1076-1083. doi:10.1001/jamapsychiatry.2013.258.
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Importance  Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects.

Objective  To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission.

Design  Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences.

Setting  Participants were recruited from the community and assessed at a university laboratory.

Participants  A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years).

Main Outcomes and Measures  Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence.

Results  There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20).

Conclusions and Relevance  Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability than previously detected in twin studies and indicates that sibling rather than parent-child similarity indexes important environmental risk factors for externalizing disorders.

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Figure 1.
Family Transmission of Externalizing Disorders

All path coefficients are standardized and are the weighted mean across the family types. All paths greater than 0.10 are significant at P < .01. The latent externalizing variables represent the general liability factors that contribute to each disorder (adult antisocial behavior [AAB], alcohol dependence [ALD], conduct disorder [CD], drug dependence [DRG], and nicotine dependence [NCD]). The smaller circular variables associated with each disorder are the residual variances and represent all liability factors that are specific to each disorder and unrelated to the general externalizing liability. The double-headed arrows linking the mother and father externalizing factors (EXTs) to the offspring (sibling) EXTs represent the general transmission effects. The double-headed arrows linking the sibling 1 and sibling 2 EXTs index sibling similarity for the general externalizing liability. These paths were allowed to vary across monozygotic (MZ) twins, dizygotic (DZ) twins and nontwin biological siblings, and adoptive siblings. The double-headed arrows linking the residual variances for CD, ALD, NCD, and DRG across siblings represent disorder-specific liability factors that increase sibling similarity but are independent of the general EXT. Correlations among the residual variances are from left to right for MZ twins, DZ twins and nontwin biological siblings, and adoptive siblings. To reduce the Figure’s complexity, we did not depict a small but statistically significant specific effect for maternal NCD (biological mothers: r = 0.11; 95% CI 0.06 to 0.17; adoptive mothers: r = 0.03; 95% CI, −0.03 to 0.08). If included, this would be a double-headed arrow linking the residual variance of maternal NCD to residual variance of sibling 1 and sibling 2 NCD.

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Figure 2.
Biometric Model of Genetic and Environmental Influences on Externalizing

All path coefficients are standardized and 95% CIs are given. All coefficients that do not include 0 are significant. The percentage of variance accounted for by a given variable in another variable can be determined by squaring the path coefficient on the path connecting the first variable to the second variable. The sum of the squared loadings (effects from the general externalizing factor as well as the specific additive genetic [A], shared environmental [C], and nonshared environmental [E] influence loadings) equals 1.0. The total effect for A, C, and E can be calculated by summing the general effect (squared loading for a given disorder multiplied by the squared A, C, and E loadings on the externalizing factor) and the specific effect (squared A, C, or E specific effect on a given disorder). Using conduct disorder as an example, a2 = general(0.612 × 0.502) + specific(0.492) = 0.33; c2 = general(0.452 × 0.502) + specific(0.432) = 0.24; e2 = general(0.442 × 0.502) + specific(0.622) = 0.43.

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