and dependence (reviewed in (36), Supplementary Table 1). Additional instances where the influence of genetic variation on function may depend on gene-environment interactions have been studied. The association between increased 5-HTT expression and low levels of response to alcohol as well as increased alcohol intake has been reported in individuals with two copies of the L-allele of 5-HTTLPR, and a similar effect was also observed among carriers of the S-allele that have been exposed to early developmental stress (37). As such, the presence of gene-environment interactions may potentially confound the interpretation of genetic association studies, account for part of the ‘missing heritability’, and contribute to the lack of reproducibility between studies. However, in the majority of cases the main genotype effect should still be observed regardless of environmental influences if the study is sufficiently powered.
