A high profile report of a G×E effect on the development of depression involves an interaction between stressful life events and a functional, repeat length polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) on chromosome 17.16 SLC6A4 encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The short (S) allele of 5-HTTLPR is associated with less transcription of the serotonin transporter compared to the long (L) allele.17, 18 The report found that carriers of either one or two copies of the S allele of 5-HTTLPR were more likely to develop major depressive disorder, increased depressive symptoms, and suicidality in response to childhood maltreatment or other stressful life events than were individuals homozygous for the L allele. Furthermore, there was evidence of a dose-response relationship, with risk of depression higher amongst those with two copies of the S allele compared to individuals with only one copy in the presence of stress. This G×E interaction report has had considerable influence on the field; it has been cited over 4000 times and over one hundred publications have investigated the combined impact of 5-HTTLPR variation and stress on risk for depression.
