No abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

RAUMATIC STRESS IS A SIGNIFIcant public health problem 1 that frequently results in a distinctive pattern of persistent and disabling psychological and physiological symptoms. 2,3 Once thought to be primarily limited to soldiers in combat, posttraumatic stress disorder (PTSD) is now recognized in civilians, including those who have experienced natural disasters, physical and sexual assault, fire, motor vehicle and other serious trauma, as well as those who have witnessed inflicted injury or death. Exposure to a traumatic event is common, estimated in the range of 5% to 35% annually, with a lifetime exposure to 1 or more traumatic events occurring in more than 50% of the US population. 1 The clinical presentation of PTSD is characterized by moderate-to-severe symptoms in 3 separate domains: reexperiencing (intrusive thoughts, nightmares, flashbacks, images, or memories), emotional numbing and avoidance (flattened affect or detachment, loss of interest and motivation, and avoidance of any activity, place, person, or topic associated with the trauma); and Author Affiliations and Financial Disclosures are listed at the end of this article.