International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Research (part of Springer Nature)
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.
Description
CITATION: Nievergelt, C. M., et al . 2019. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications, 10:4558, doi:10.1038/s41467-019-12576-w.
The original publication is available at https://www.nature.com
The original publication is available at https://www.nature.com
Keywords
Post-traumatic stress disorder -- Genetic aspects -- Risk factors, Post-traumatic stress disorder -- Sex differences -- Risk factors, Meta-analysis
Citation
Nievergelt, C. M., et al . 2019. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications, 10:4558, doi:10.1038/s41467-019-12576-w