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.

Violence against women is a major public health concern,¹ contributing to high levels of morbidity and mortality worldwide.² Our study examines the mental health associations of 4 types of violence that are commonly perpetrated against women, namely physical forms of intimate partner violence (IPV), rape, other forms of sexual assault, and stalking, and were specifically included in the Australian National Mental Health and Well-being Survey. These 4 types of violence are referred to collectively herein as gender-based violence (GBV).³

Posttraumatic stress disorder (PTSD) affects as many as 1 in 4 people who experience traumatic events¹ and contributes to marked functional disability, health impairment, and social dysfunction.² Despite the attention this condition has received, the fundamental nature of the syndrome is poorly understood. Although most survivors of trauma experience elevated stress responses in the immediate aftermath of trauma exposure, most of these reactions abate in the ensuing period, and only a minority of survivors develops a long-standing disorder.³ This process potentially involves fear conditioning at the time of trauma, resulting in overconsolidation of trauma memories.⁴