Apolipoprotein E variants and genetic susceptibility to combat-related post-traumatic stress disorder: a meta-analysis

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Apolipoprotein E (APOE) has recently been studied as a risk factor for association with developing combat-related post-traumatic stress disorder (PTSD) in the military population. These studies have yielded inconsistent findings. The present study carried out a meta-analysis to establish whether the APOE polymorphism confers increased susceptibility to combat-related PTSD.


PubMed, Medline, Embase, PsycInfo, and Google Scholar were searched for potential publications relating to patients with PTSD in military settings with combat exposure. Studies provided proper PTSD screening and genotype data on APOE gene variants were all considered for selection in the review. A random-effect model was used to calculate the pooled effect size (Cohen’s d) and summary statistics. Sensitivity analyses and meta-regression were used to assess the between-study heterogeneity. Egger’s test and rank-correlation test were also carried out to evaluate any potential publication bias.


Our study showed a significant association between the APOE e4 gene variant and increased risk for developing combat-related PTSD, with an overall effect size of d equal to 0.28 (95% confidence interval: 0.10–0.45) for e4 carriers versus noncarriers. In contrast, no statistically significant association was found for the APOE e2 variant (d=0.59; 95% confidence interval: −0.29–1.47).


The current meta-analysis provides corroborating evidence that supports the fact that the presence of the APOE e4 polymorphism confers greater susceptibility to combat-related PTSD. Future studies with a larger sample size and better consistency in reporting standards are warranted to further evaluate these associations.

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