BACKGROUND: The apolipoprotein E (APOE) ε4 allele has been implicated in a range 
of neuropsychiatric conditions. The present research examined if the ε4 allele 
of the APOE gene moderated the effect of combat exposure on posttraumatic stress 
disorder (PTSD) among Iraq/Afghanistan-era veterans.
METHOD: Participants included 765 non-Hispanic White (NHW) and 859 non-Hispanic 
Black (NHB) Iraq/Afghanistan-era veterans. A structured interview established 
psychiatric diagnoses. Combat exposure and PTSD symptom severity were assessed 
via self-report.
RESULTS: The most common lifetime diagnoses were depression (39.2%), PTSD 
(38.4%), and alcohol dependence (24.38%). After correcting for multiple 
comparisons, no significant effects were observed on any of the outcomes among 
the NHW sample; however, within the NHB sample, significant gene × environment 
(G × E) interactions were observed for lifetime PTSD (P = .0029) and PTSD 
symptom severity (P = .0009). In each case, the APOE ε4 allele had no effect on 
the outcomes when combat exposure was low; however, when combat exposure was 
high, an additive effect was observed such that ε4 homozygotes exposed to high 
levels of combat reported the highest rates of PTSD (92%) and the worst symptom 
severity scores on the Davidson Trauma Scale (M = 79.5).
CONCLUSIONS: Although preliminary, these findings suggest that the APOE ε4 
allele, in conjunction with exposure to high levels of combat exposure, may 
increase veterans' risk for developing PTSD.