Identifying differential interactions of traumatic experiences with genetic risk for posttraumatic stress disorder

Gene-environment interactions are critical for understanding the genetics of PTSD, although it remains unclear how they differ across traumas. Using data from the UK Biobank and GLAD-EDGI-COPING (N=144,702), we conducted gene-environment interaction analyses incorporating eleven trauma measures. We analysed polygenic risk scores, specific genes, and specific genetic variants. Childhood traumas had stronger associations with PTSD symptoms and greater gene-environment interactions than adulthood traumas on average. Interaction patterns varied across genes and variants, with many of the leading genes for PTSD (e.g. ANAPC, FAM120A, SGCD) having particularly great interactions with certain traumas. Several genes (DTX4, PSMD12, TYW3, ZNF660) demonstrated stronger interactions with all childhood or all adulthood traumas. Our results suggest genetic influences on PTSD risk vary by trauma type and are most pronounced for childhood traumas. To accommodate the moderating effect of trauma type, genomic research on PTSD should incorporate trauma exposure information.