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.
Highlights
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified
We report meta-analyses of GWAS from the PGC-PTSD Freeze 2 (PGC2), comprised of an ancestrally diverse group of 206,655 participants from 60 different PTSD studies, ranging from clinically deeply characterized, small patient groups to large cohorts with self-reported PTSD symptoms (Supplementary Data 1)
We further examined sex differences in heritability in different subsets of the data: the PGC freeze 2 samples (PGC2) data without the UK Biobank and the UK Biobank (UKB) by itself, which comprises a large proportion of PGC2
Summary
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. We demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, 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. PTSD) published results from a large GWAS on PTSD, involving a trans-ethnic sample of over 20,000 individuals, approximately 5000 (25%) of whom were cases[10] With this limited sample size, no individual variants exceeded genome-wide significance; significant estimates of SNP heritability and genetic correlations between PTSD and other mental disorders such as schizophrenia were demonstrated for the first time
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
