(A) The significance level of each of the five OPRL1 SNPs examined is shown as “log(Pinteraction)” for the interaction of each genotype and level of self-reported child abuse [using the Childhood Trauma Questionnaire (CTQ)]. For a Bonferroni-corrected P value of 0.01 (for five SNPs), the log(P) would be 2. We find that the rs6010719 SNP survives correction for the interaction test at P ≤ 0.005. (B) Location of SNPs within the OPRL1 gene (average 3.5-kb inter-SNP interval) and location of the gene on chromosome 20. (C) Specific interactions of the G allele carriers (GG, GC) versus CC allele carriers of the rs6010719 SNP in OPRL1, demonstrating that G allele carriers who have experienced greater trauma are at higher risk for PTSD symptoms (F1,1847 = 10.5; P < 0.001, UNIANOVA). Additionally, we found no interactions between this SNP and variables such as sex, age, or substance abuse that predicted PTSD symptoms (all P values >0.1). (D) G allele carriers of the rs6010719 SNP (n = 49) showed no discrimination between CS+ (danger signal) and CS− (safety signal) measured by the FPS response. In contrast, individuals of the CC genotype (n = 70) showed normal discrimination (interaction: *P < 0.05, ***P ≤ 0.001, ANOVA). (E) OPRL1 mRNA is highly expressed in the human central amygdala [picture modified from Allen Brain Atlas (, )]. The arrow indicates the central amygdala. (F) (Left) Within-group random-effects analysis showed enhanced bilateral amygdala activation in response to fearful versus neutral face stimuli in all participants, irrespective of genotype (local maximum for left amygdala: Z = 4.32; x, y, z = −32, −8, −16; Pcorr < 0.05; local maximum for right amygdala: Z = 3.12; x, y, z = 28, −4, −28; Pcorr < 0.05). (Right) For fearful versus neutral face stimuli, G carriers (n = 10) have increased functional connectivity between amygdala (seed region) and right posterior insula, relative to CC allele carriers (n = 19) (Pcorr < 0.05). Results are overlaid on a representative structural anatomical image in standard Montreal Neurological Institute space.