Brain trauma affects millions. Learn about traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and how they impact civilians and Veterans.
Cohen Veterans Bioscience is a non-profit 501(c)(3) biomedical research and technology organization dedicated to advancing brain health by fast-tracking precision diagnostics and tailored therapeutics.
Our approach is to build enabling platforms with strategic partners and to adopt a team science approach to fast-track solutions in years, not decades.
Landmark Study Identifies Six Genetic Markers of Post-Traumatic Stress Disorder (PTSD) Risk
Findings Implicate Novel Biological Pathways in PTSD, Advancing Understanding of Prevention and Treatment.
Collaborative Effort Greatly Accelerated, Expanded Scope of Study to Examine More Than 30,000 Multiethnic PTSD Cases and 170,000 Controls
Cohen Veterans Bioscience (CVB), a non-profit organization dedicated to advancing brain health through data driven science, and the Stanley Center for Psychiatric Research at the Broad Institute at MIT and Harvard, announce findings from a study published in Nature Communications that identifies three genome wide genetic loci associated with PTSD risk.
Post-traumatic stress disorder (PTSD) is the most commonly occurring and seriously impairing disorder that occurs after exposure to traumatic events, such as combat, sexual assault, and natural disaster. According to the World Health Organization, an estimated 3.6% of the world’s population has suffered from post-traumatic stress disorder (PTSD) in a given year.Trauma-related disorders are also a major contributor to risk for suicide a devastating outcome affecting as many as 20 U.S. veterans per day.
The risk of developing PTSD after experiencing trauma is heritable, but robust genetic markers had not yet been identified by previous genome-wide association studies (GWAS). Through this global collaboration, analyses were conducted on data and samples collected from multi-ethnic cohorts that included over 30,000 PTSD cases and 170,000 controls. The study, International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci1, was able to demonstrate significant genetic correlations across 60 PTSD cohorts, including a UK Biobank dataset. In this largest GWAS meta-analysis of PTSD to date, a total of three genome-wide significant risk loci were identified, two in European and one in African-ancestry analyses. When analyzing the data based on sex, an additional three risk loci were identified in men two in European and one in African ancestry. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, was associated with PTSD. Consistent with previous reports, single nucleotide polymorphisms (SNP)-based heritability estimates for PTSD range between 5-20%. These heritability estimates are similar to rates observed for major depression.
Researchers also generated a polygenic risk score (PRS) for PTSD based on their findings. While larger sample sizes are needed to explore the observed variance and improve sensitivity of the PRS, researchers confirmed that the PRS is highly predictive of re-experiencing symptoms” a core feature of PTSD in an external dataset from the Million Veterans Program, although specific risk loci did not replicate in this population.
These results demonstrate that genetic variation contributes to the biology of differential risk for PTSD and provide an essential foothold to advance our broader goal of understanding disease pathways for preventing and treating the devastating impact of PTSD, including suicide.
Major funding and program management support for the study was provided by CVB in partnership with the Stanley Center for Psychiatric Research and collaboration with the Psychiatric Genetics Consortium PTSD Working Group. This endeavor also included the creation of a PTSD genetics database devoted exclusively to the analysis of tens of thousands of DNA samples collected from more than 130 global research centers, which will allow for ongoing translational research.
These findings underscore the role and importance of better understanding the biological mechanisms and genetic risks associated with PTSD to help drive breakthroughs in prevention and treatment,” says Magali Haas, MD, PhD, CEO & President of CVB. This landmark study also is a testament to the power of team science to dramatically accelerate progress by expanding access to PTSD cases, and to provide genetically-diverse samples for robust genetic results.”
A critical feature for the success of this program was the centralization and access to high-performance bioassays and analytic pipelines supported by the Broad Institute. In the spirit of open-science, the full meta-analyses summary statistics are available for download from the Psychiatric Genomics Consortium.
1 Nievergelt C. et al. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci Nature Communications (2019). 10.1038/s41467-019-12576-w
2 Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in> 165,000 US veterans. Nature Neuroscience. 2019 Sep;22(9):1394-401.
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Cohen Veterans Bioscience is a non-profit 501(c)(3) biomedical research and technology organization dedicated to advancing brain health by fast-tracking precision diagnostics and tailored therapeutics.
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