Summary: A new large-scale genetic study shows molecular evidence that inherited variation contributes to the risk of developing posttraumatic stress disorder (PTSD) after exposure to trauma.
Source: Harvard T.H. Chan School of Public Health
Major new analysis from the Psychiatric Genomics Consortium shows molecular genetic influences on PTSD risk and reveals sex differences in heritability.
A collaborative genome-wide study by the Psychiatric Genomics Consortium (PGC) provides the strongest molecular genetic evidence to date that inherited variation affects whether a person develops PTSD after trauma. The analysis pooled genome-wide data from more than 20,000 people across 11 multi-ethnic studies worldwide to estimate heritability, evaluate genetic overlap with other psychiatric disorders, and search for specific genetic risk loci.
PTSD is a common and disabling psychiatric condition that can follow traumatic events. Symptoms often include intrusive re-experiencing of trauma, avoidance of trauma-related stimuli, and persistent hyperarousal. In the United States, lifetime PTSD prevalence estimates indicate that roughly one in nine women and one in twenty men will meet diagnostic criteria at some point, with major societal consequences including increased suicide risk, hospitalization, and substance misuse.
The PGC-PTSD study used genome-wide single-nucleotide polymorphism (SNP) data to produce the first reliable molecular estimate of PTSD heritability in a large sample. Among European-American women, the SNP-based heritability (h2SNP) was estimated at around 29%, a level comparable to heritability estimates for other major psychiatric disorders. In contrast, the study found substantially lower and statistically indistinguishable-from-zero heritability for European-American men in this sample. These sex differences point to complex interactions among genetics, sex, and trauma exposure that influence PTSD risk.
Beyond estimating heritability, the researchers tested genetic correlations between PTSD and other psychiatric disorders. They found strong evidence of shared genetic risk between PTSD and schizophrenia and more modest shared genetic influences with bipolar disorder and major depressive disorder. These cross-disorder genetic links suggest overlapping biological pathways that contribute to vulnerability across multiple forms of mental illness.
No individual SNP reached genome-wide significance in the combined transethnic meta-analysis, and the study did not replicate previously reported single-variant associations. However, the authors emphasize that the SNP-level summary statistics released with the study provide a valuable resource for polygenic risk prediction, genetic correlation analyses, and future meta-analyses that include larger and more diverse samples. The dataset notably includes summary statistics from roughly 10,000 African American participants, contributing to efforts to increase ancestral diversity in psychiatric genomics.
Study authors highlight clinical and research implications. Early preventive interventions after trauma can reduce PTSD onset, but they are often too resource-intensive to offer universally. Better genetic risk stratification could ultimately help target preventive care to those at greatest molecular risk, while also advancing understanding of the biological mechanisms underlying PTSD.
Key contributors to the work include researchers from the Psychiatric Genomics Consortium PTSD Working Group, investigators at Harvard T.H. Chan School of Public Health, the Broad Institute, and collaborating institutions. Andrea Roberts from Harvard Chan School’s Department of Social and Behavioral Sciences is a co-author.
Funding: The study was supported by the National Institute of Mental Health (U01MH094432), Cohen Veterans Bioscience, One Mind, and the Stanley Center for Psychiatric Research.
Original research: Duncan LE, Ratanatharathorn A, Aiello AE, Almli LM, Amstadter AB, Ashley-Koch AE, et al. “Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differences in Heritability.” Molecular Psychiatry. Published online April 25, 2017. doi:10.1038/MP.2017.77
Abstract (summary)
The Psychiatric Genomics Consortium–PTSD group combined genome-wide case–control molecular genetic data from 11 multiethnic studies (total N ≈ 20,730) to quantify PTSD heritability, evaluate shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder, and search for PTSD risk loci. The analysis reports an SNP-based heritability of about 29% in European-American women—similar to estimates for schizophrenia—and substantially lower estimates in European-American men. The study documents strong genetic overlap between PTSD and schizophrenia and smaller overlaps with bipolar disorder and major depressive disorder. While no SNPs achieved genome-wide significance in the overall meta-analysis, the public release of SNP summary statistics—including a substantial African-American sample—provides a foundation for polygenic risk scoring, genetic correlation studies, and future research that increases ancestral diversity and statistical power to identify specific risk loci.
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