Because parents provide the environmental context for the family and transmit genetic makeup to their offspring, the genetic and environmental processes responsible for associations between family risk factors and offspring adjustment are confounded. Social scientists typically use statistical controls to account for ‘third’ variables that influence both characteristics, but family studies cannot account for unmeasured genetic or environmental confounds.

The Children of Twins (CoT) Design [7, 13]. Using children of identical twins can determine if a parental characteristic has an environmental association with a child behavior or whether the intergenerational relation is confounded by selection factors. When children of fraternal twins are included, the design is able to reveal whether confounds are genetic or environmental in origin⁵.

The CoT Design is best known for its use with studying dichotomous environmental risk factors, such as a diagnosis of a psychiatric disorder⁶. For example, the children of schizophrenic parents are at higher risk for developing the disorder than the general population. In order to elucidate the genetic and environmental mechanisms responsible for the intergenerational association, researchers compare the rates of schizophrenia in the offspring of discordant pairs of twins (one twin is diagnosed with the disorder and one is not). A comparison between the children of affected (diagnosed with schizophrenia) identical twins and their unaffected (no diagnosis) cotwins is the initial step in trying to understand the processes through which the intergenerational risk is mediated. Because offspring of both identical twins share the same genetic risk associated with the parental psychopathology from the twins, any difference between the offspring is associated with environmental processes specifically related to the parental psychopathology (see below for a discussion of the influence of the nontwin parent). Effectively, the CoT Design provides the best control comparison group because children with schizophrenia are compared with their cousins who share the same genetic risk associated with schizophrenia and any environmental conditions that the twins share. If offspring from the unaffected identical twin have a lower prevalence of schizophrenia than offspring of the affected identical twin, the results would suggest that the experience of having schizophrenic parent has a direct environmental impact on one’s own risk for schizophrenia

…The most well-known application of the design explored the intergenerational association of schizophrenia using discordant twins⁶. Offspring of schizophrenic identical cotwins had a morbid risk of being diagnosed with schizophrenia of 16.8, whereas offspring of the unaffected identical cotwins had a morbid risk of 17.4. Although the offspring in this later group did not have a parent with schizophrenia, they had the same risk as offspring with a schizophrenic parent. The results effectively discount the direct causal environmental theory of schizophrenia transmission. The risk in the offspring of the unaffected identical twins was 17.4, but the risk was much lower (2.1) in the offspring of the unaffected fraternal cotwins. This latter comparison suggests that genetic factors account for the association between parental and offspring schizophrenia.

Similar findings were reported for the transmission of bipolar depression¹. In contrast, the use of the CoT to explore transmission of alcohol abuse and dependence from parents to their offspring highlighted role of the family environment⁸.

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