In the largest and most diverse genetic study to date of post-traumatic stress disorder (PTSD), scientists reveal that PTSD has a strong genetic component similar to other psychiatric disorders.
The findings are published in the journal Nature Communications.
Despite much research, it has remained unclear why some people go on to develop PTSD after a traumatic event while others do not. Some researchers suggest that the disorder is only a social construct, but other studies point to the fact that genetics may be involved.
In the new study, researchers from the University of California (UC) San Diego School of Medicine and more than 130 additional institutions participating in the Psychiatric Genomics Consortium suggest that genetics may account for between five and 20 percent of the variability in PTSD risk following exposure to a traumatic event.
“Our long-term goal is to develop tools that might help clinicians predict who is at greatest risk for PTSD and personalize their treatment approaches,” said the study’s first and corresponding author Caroline Nievergelt, Ph.D., associate professor of psychiatry at UC San Diego School of Medicine and associate director of neuroscience in the Center of Excellence for Stress and Mental Health at the Veterans Affairs San Diego Healthcare System.
“We can’t always protect people from trauma. But we can treat them in the best ways possible, at the best time.”
The findings show that, like other psychiatric disorders and many other human traits, PTSD is highly polygenic, meaning it is associated with thousands of genetic variants throughout the genome, each making a small contribution to the disorder.
According to the findings, six genomic regions called “loci” contain variants strongly associated with disease risk, providing some clues about the biological pathways involved in PTSD.
“Based on these findings, we can say with certainty that there is just as much of a genetic component to PTSD risk as major depression and other mental illnesses,” said senior author Dr. Karestan Koenen, associate member of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.
“Our limited ability to study the living human brain and uncover the biological roots of PTSD has contributed to the lack of treatments and the stigma around this debilitating condition. Genetics helps us make new discoveries, find opportunities for new therapies, and counter that stigma,” she said.
Since many behavioral traits and psychiatric disorders have some shared genetic factors, the researchers also looked for genetic correlations between PTSD and 235 other disorders, behaviors and physical traits. They discovered significant overlap with 21, including depression, schizophrenia, neuroticism, insomnia, asthma and coronary artery disease.
“Similar to other mental disorders, the genetic contribution to PTSD correlates with that for many other traits,” said Koenen, who is also professor of psychiatric epidemiology in the Harvard T.H. Chan School of Public Health. “Further research is needed to determine what this means — whether some of the same genes that influence risk for PTSD also influence risk for other diseases like, for example, depression.”
To conduct the study, the team collaborated with the Psychiatric Genomics Consortium’s PTSD working group and Cohen Veterans Bioscience, a non-profit organization dedicated to accelerating PTSD and traumatic brain injury research.
The team built an international network of more than 200 researchers, assembling data and DNA samples from more than 60 groups of people with PTSD and control subjects, including the UK Biobank.
The data included more than 200,000 people, which is 10 times larger than the first Psychiatric Genomics Consortium PTSD study, published in 2017. The study group is also the most ancestrally diverse for any psychiatric genetics study to date, with more than 23,000 people with PTSD of European ancestry and more than 4,000 of African ancestry. It also included both civilians and members of the military.
“Our study is distinguished by the fact that it’s international and is highly diverse,” Nievergelt said. “There’s greater representation here than in most studies to date.”
The team used the data to conduct a genome-wide association study (GWAS), using statistical tests to measure the effect of common genetic variants at millions of points across the genome on someone’s likelihood of developing PTSD.
The study uncovered DNA variants at six loci that were significantly tied to PTSD risk. Three of the six loci were specific to certain ancestral backgrounds — two European and one African — and three were only detected in men.
The six loci hint that inflammatory and immune mechanisms may be at play in the disorder, which is consistent with findings from previous research.
Overall, the researchers conclude that PTSD’s heritability — the level of influence genetics has on the variability of PTSD risk in the population — is between five and 20 percent, with some variability by gender. These findings were similar across different ancestral groups.
The research team also developed a polygenic score that could potentially predict one’s risk of developing PTSD following a traumatic event. Polygenic scores take into account the effects of millions of genetic variations and create a measure that can predict a person’s risk of developing a certain trait or disorder.
The team tested their scores on data from men in the UK Biobank dataset, finding that those with the highest scores had 0.4-fold greater odds of developing than those with the lowest scores.
Similarly, when applied to data from the Million Veterans Program — a study of how genes, lifestyle and military exposures impact health and illness — individuals with the highest scores had a significant increase in re-experiencing traumatic memories — a key PTSD symptom.
The researchers assert that polygenic scores are not ready for clinical use. Even larger studies with more diverse datasets are needed to improve the accuracy of PTSD prediction and confirm the genetic findings.