results in higher levels of phenylalanine than normal which in turn causes mental retardation. The risk factor in Model B in contrast has a direct effect on disease susceptibility which is amplified by the genetic susceptibility. Model C depicts the inverse, where the genetic susceptibility directly effects disease while the risk factor amplifies this effect. In each independent situation, the factor directly effecting the disease can cause disease by itself. Model D differs as neither factor in this situation can effect disease risk, however, when both genetic susceptibility and risk factor are present the risk is increased. For example, the G6PD deficiency gene when combined with fava bean consumption results in hemolytic anemia. This disease does not arise in individuals that eat fava beans and lack G6PD deficiency nor in G6PD-deficient people who do not eat fava beans. Lastly, Model E depicts a scenario where the environmental risk factor and genetic susceptibility can individually both influence disease risk. When combined, however, the effect on disease risk differs. The models are limited by the fact that the variables are binary and so do not consider polygenic or continuous scale variable scenarios. Methods of analysis Traditional genetic designs Adoption studies Adoption studies have been used to investigate how similar individuals that have been adopted are to their biological parents with whom they did not share the same environment with. Additionally, adopted individuals are compared to their adoptive family due to the difference in genes but shared environment. For example, an adoption study showed that Swedish men with disadvantaged adoptive environments and a genetic predisposition were more likely to abuse alcohol. Twin studies Using monozygotic twins, the effects of different environments on identical genotypes could be observed. Later studies leverage biometrical modelling techniques to include the comparisons of dizygotic twins to ultimately determine the different levels of gene expression in different environments. Family studies Family-based research focuses on the comparison of low-risk controls to high risk children to determine the environmental effect on subjects with different levels of genetic risk. For example, a Danish study on high-risk children with mothers who had schizophrenia depicted that children without a stable caregiver were associated with an increased risk of schizophrenia. Molecular analyses Interaction with single genes The often used method to detect gene–environment interactions is by studying the effect a single gene variation (candidate gene) has with respect to a particular environment. Single nucleotide polymorphisms