In a prospective-longitudinal study of a representative birth cohort, Caspi et al. (2003) reported that variation in a promoter-linked polymorphism in SLC6A4, which encodes the serotonin transporter, moderated the influence of stressful life events on depressive symptoms, depression diagnosis, and suicidality. A similar G × E approach was used to examine the interaction between this 5-HTTLPR polymorphism and alcohol-related risk. To date, three studies have shown that the 5-HTTLPR “s” allele (which is associated with lower expression and functionality), in the context of various environmental stressors, is associated with increased alcohol consumption (Nilsson et al. 2005; Covault et al. 2007; Kaufman et al. 2007). This augments meta-analytic findings of a main effect of the s allele of 5-HTTLPR on risk of AD (Feinn et al. 2005). However, there are variable findings in relation to the G × E effect. The COGA group (Dick et al. 2007b) failed to replicate a moderating effect of environmental stress on the association of this polymorphism with AD. Recently, a German group studying participants in the Mannheim study of children at risk (Laucht et al.
