A 2023 multi-ancestry meta-analysis of genome-wide association studies is the direct result of the Global PTSD Genetics Initiative jointly founded in 2015 by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Research at Broad Institute, and the Psychiatric Genomics Consortium.

Analyzing data across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases), we identified 95 genome-wide significant loci (80 novel).

This new research further validates that heritability is a central feature of PTSD and reinforces our understanding that there is a genetic component contributing to the complexity of PTSD.

Understanding the genetic risk factors for PTSD could have profound implications on improving patient care:

• Genes identified in this study may provide insight into biological mechanisms that contribute to PTSD, and may be fruitful for targeted drug discovery advancement.
• Genetic stratification based on identified genes may be used to partition trauma patients indicating those most at risk for developing PTSD.
• Baseline genetic tests may identify individuals most susceptible to PTSD for proactive treatment.

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,” said Dr. Caroline M. Nievergelt, Professor of Psychiatry at 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.

Genetics are Helpful to Better Understand PTSD

In 2019, Cohen Veterans Bioscience (CVB) convened and funded a global network of researchers and clinicians from more than 60 organizations including the Psychiatric Genomics Consortium and Stanley Center for Psychiatric Research at the Broad Institute at MIT and Harvard to drive the PTSD genetics field forward.

With a genome-wide association study of PTSD, using a multi-ethnic cohort including more than 30,000 PTSD cases, 170,000 controls, more than ten times the size of any previous analysis, six genetic markers for PTSD risk were discovered.

The study, International Meta-Analysis of PTSD Genome-Wide Association Studies, made significant strides in our genetic understanding of PTSD:

• This study demonstrated significant genetic correlations across 60 PTSD cohorts, including participants in the UK Biobank.
• 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, heritability estimates for PTSD based on single nucleotide polymorphisms (SNP) range between 5-20% – which are similar to rates observed for major depression.