GxE effects of FKBP5 and traumatic life events on PTSD: A meta-analysis

Abstract

Background: Twin studies have demonstrated that both genetic and environmental factors influence risk for posttraumatic stress disorder (PTSD), and there is some evidence supporting the interplay of genes and environment (GxE). Many GxE studies within the PTSD literature have focused on genes implicated in the stress response system, such as FK506 binding protein 51 (FKBP5). Given inconsistencies across GxE literature as a whole, a meta-analysis to synthesize results is warranted.

Methods: Studies were identified through PubMed and PsycINFO. A meta-analysis was conducted using a random effects model in the MAc package in R. Heterogeneity of the effect size distribution was examined with Cochran's Q statistic. A Simes procedure was used to test the gene-level GxE effect for FKBP5 interacting with trauma.

Results: A significant gene-level GxE gene effect was demonstrated for FKBP5 when pooled across all four examined variants (rs1360780, rs3800373, rs9296158, rs9470080) when interacting with trauma exposure on PTSD. Significant large GxE effect sizes were also found for each independent variant. There was no evidence for heterogeneity of variance.

Limitations: Limitations include reduced power for detecting variability across moderators, potential bias due to failure of meta-analyzed studies to account for two-way covariate x gene and covariate x environment influences, and a high false discovery rate that is characteristic of GxE analyses.

Conclusions: This is the first study to quantify an overall gene-level effect of FKBP5 in a GxE analysis of PTSD, evidence which may be used to address current issues in the FKBP5 GxE literature (e.g., disparate variants, low sample sizes and power), as well as inform follow-up functional research.

Keywords: Alcohol; FKBP5; GxE; Posttraumatic stress; Trauma.

Fig. 1.

Flow diagram showing search and selection of studies for GxE meta-analysis of FKPB5.

Fig. 2.

Leave-one-out plot.