The role of the CpG island may be particularly critical in this pathogenesis. Although it is commonly appreciated that a substantial portion of gene activity is contributed by heritable factors, over the past several years it has also become apparent that gene-environment interactions (GxE), which are defined as environmental effects whose impact is dependent on gene status, also make substantial contributions to neuropsychiatric illness [Moffitt et al., 2005]. In particular, some [Caspi et al., 2003; Kendler et al., 2005], but not all studies [Surtees et al., 2006], have suggested that GxE effects at SLC6A4 are particularly pivotal in the development of MD. Because gene elements such as CpG motifs are potentially modifiable by environmental factors, they may represent a physical substrate for these GxE effects to become manifest. If so, by characterizing the regulatory elements of SLC6A4 responsible for these interactions, it may be possible to identify vulnerable individuals and design more effective, personalized interventions for certain forms of behavioral illness and integrate the effects of these elements into a more comprehensive understanding of the biology that underlies vulnerability to neuropsychiatric illness.
