NEW YORK, April 18, 2024 – The Global PTSD Genetics initiative founded in 2015 by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Research at Broad Institute, and the Psychiatric Genomics Consortium today announces a pivotal milestone in the genetics of post-traumatic stress disorder (PTSD) has been achieved and published in Nature Genetics on April 18,2024.

This multi-ancestry meta-analysis of genome wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 ad mixed individuals with African and Native American ancestry (13,624 cases) identified 95 genome-wide significant loci, including 80 novel loci. Convergent multiomic approaches identified 43 potential causal genes, including modulators of neurotransmitters, ion channels, axon guidance, and synapses.  Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen the understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, hyperarousal, avoidance, and negative alterations in cognition and mood that can become persistent for some individuals after traumatic event exposure. Approximately 5.6% of trauma-exposed adults worldwide experience PTSD during their lifetimes, and rates are higher in those with high levels and certain types of trauma exposure such as combat survivors and assault victims.

The most recent effort from the PTSD Consortium is a tour-de-force in human genetics, that would not have been possible without the generous contribution of more than a million individuals participating in 88 studies. The substantial efforts of a large scientific team led by Dr. Nievergelt were responsible for carefully conducting genetic analyses and insightfully validating the heritable nature of PTSD.

‘This discovery firmly validates that heritability is a central feature of PTSD based on the largest PTSD genetics study conducted to date and reinforces there is a genetic component that contributes to the complexity of PTSD” Dr. Caroline M Nievergelt Professor of Psychiatry, University of California, San Diego.

With this early genetic architecture in hand, carefully reasoned discovery and preclinical efforts can be initiated to begin to mechanistically untangle cellular aspects that contribute to the complex clinical phenotypes that currently define PTSD.

“This meta-analysis firmly demonstrates that genetic variation contributes to the biology of differential risk for PTSD and provides an essential foothold to advance our broader goal of understanding disease pathways for preventing and treating the devastating impact of PTSD.” Cohen Veterans Bioscience Founder and Board Chair, Magali Haas, MD, PhD. 

By integrating putative genetically identified pathways and known therapies with application to other neuropsychiatric disorders, support for additional therapeutics may emerge for PTSD. This research reinforces that there is a genetic component that contributes to the complexity of PTSD and provides the opportunity to remove the stigma often related to PTSD diagnosis.

Major financial support for the PTSD-PGC was provided by the Cohen Veterans Bioscience, Stanley Center for Psychiatric Research at the Broad Institute, and the National Institute of Mental Health (NIMH; R01MH106595, R01MH124847, R01MH124851).

Statistical analyses were carried out on the NL Genetic Cluster computer (URL) hosted by SURFsara. Genotyping of samples was supported in part through the Stanley Center for Psychiatric Genetics at the Broad Institute of MIT and Harvard.

This work would not have been possible without the contributions of the investigators who comprise the PGC-PTSD working group, and especially the more than 1,307,247 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators.

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