Gene X environment interactions at the serotonin transporter locus.
BACKGROUND
Although it is universally accepted that human disease and behavior depend upon both environmental and genetic variation, a view supported by family and twin studies, examples of environmental interactions with genes identified at the molecular level (G x E) are not so well established.


METHODS
We carried out a systematic review and meta-analysis of the serotonin transporter (5-HTTLPR) polymorphic region x stressful life event (SLE) literature and investigated to what extent the main effects reported in this literature are consistent with a number of G x E hypotheses. Our aim was to provide a framework in which to assess the robustness of the claim for the presence of an interaction.


RESULTS
The results from our systematic review and meta-analysis indicate that the main effect of 5-HTTLPR genotype and the interaction effect between 5-HTTLPR and SLE on risk of depression are negligible. We found that only a minority of studies report a replication that is qualitatively comparable to that in the original report.


CONCLUSIONS
Given reasonable assumptions regarding likely genetic and environmental effect sizes, our simulations indicate that published studies are underpowered. This, together with other aspects of the literature, leads us to suggest that the positive results for the 5-HTTLPR x SLE interactions in logistic regression models are compatible with chance findings.
Munafò
Marcus R
MR
Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom. marcus.munafo@bristol.ac.uk
Durrant
Caroline
C
Lewis
Glyn
G
Flint
Jonathan
J
D003198:Computer Simulation; D004777:Environment; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D016015:Logistic Models; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics* / Q000523:psychology*
D050486:Serotonin Plasma Membrane Transport Proteins