Does age matter in genetics? The role of ADCYAP1R1 in sex-specific risk for posttraumatic stress disorder in trauma-exposed preadolescent children

Following trauma exposure, children are a vulnerable population and at risk for developing posttraumatic stress disorder (PTSD). A large body of research has demonstrated the impactful role of genetics in vulnerability for PTSD in adult samples; yet very little research has examined genetic risk for PTSD in children. It is unknown whether genetic associations identified in adults are true for children; replication of findings from adult samples is needed in child samples. This study investigated an estrogen-responsive variant (ADCYAP1R1) that has been well-established to confer sex-specific risk for PTSD in adult samples, but is hypothesized to function differently in children, potentially due to pubertal changes in the estrogen system. Participants were children (n = 87; 57% female) ages 7 to 11 exposed to a natural disaster. Participants were assessed for trauma exposure and symptoms of PTSD. Participants provided a saliva sample, which was genotyped for the ADCYAP1R1 rs2267735 variant. In girls, the ADCYAP1R1 CC genotype was associated with PTSD (OR = 7.30). In boys, evidence for the opposite effect emerged, with the CC genotype attenuating risk for PTSD (OR = 8.25). When investigating specific PTSD symptom clusters, an association between ADCYAP1R1 and arousal emerged. This study is the first to investigate the relationship between ADCYAP1R1 and PTSD in trauma-exposed children. Findings for girls mirrored prior research on adult women, whereas findings for boys diverged from prior research on adult men. These potential differences between children and adults in genetic vulnerability for PTSD underscore the need for more genetic studies in child samples.