Our understanding of post-traumatic stress disorder (PTSD), until now, is that it is a mental health disorder that occurs as a consequence of exposure to extreme, life-threatening stress, and/or serious injury. This exposure, by definition, is requisite for the development of PTSD, but not all those who face trauma necessarily develop it — the individual susceptibility to PTSD varies widely. Since the turn of the century, scientists have been trying to find evidence for genetic influence on PTSD risk, with the last decade witnessing concerted efforts to identify specific DNA variants that can influence one’s genetic susceptibility to develop PTSD.

New research, findings of which were published in Nature Communications, has, for the first time, identified a clear biological pathway for the mental health disorder, despite a section of science still viewing it as an entirely social construction. In the largest and most diverse genetic study of PTSD to date, scientists from the University of California, San Diego, School of Medicine and more than 130 additional institutions have concluded that genetics do, in fact, play a role in determining whether or not a person will develop PTSD, similar to the biological pathways of depression and other forms of mental illness.

“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. We can’t always protect people from trauma. But we can treat them in the best ways possible, at the best time,” Dr. Caroline Nievergelt, the study’s first author, 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, said in a press release.

In collaboration 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 study’s authors built a 12-country network of more than 200 researchers, assembling data and DNA samples from more than 20,000 people with PTSD and 170,000 control subjects (those who did not develop PTSD following trauma).

At more than 200,000 people, the latest study’s sample size is 10 times larger than the first Psychiatric Genomics Consortium PTSD study, published in 2017, and includes both civilians and members of the military. The release notes the cohort 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.”

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Putting this large database through statistical analyses, the study’s authors measured the effect of gene variants at millions of different points on chromosomes across the human genomes on someone’s chances of developing PTSD.

According to the findings, PTSD’s heritability — the level of influence genetics has on the variability of PTSD risk among people — is between 5% and 20%. Scientists found that, like other psychiatric disorders and several human traits, the risk of developing PTSD following trauma is a highly polygenic trait. This means there exist thousands of genes at different loci on different chromosomes that make tiny contributions to the disorder — and when expressed together, add up to the heritable trait. Scientists have found gene variants at six loci that were strongly associated with 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 involved in the disorder, which is consistent with findings from previous studies,” the release summarises.

Further exploring the relatively nascent belief in science that many psychiatric disorders and behavioral traits have important molecular similarities at DNA-level, the study also analyzed genetic correlations between PTSD and 235 other disorders behaviors and physical traits. They found a significant overlap with 21, including depression, schizophrenia, insomnia, asthma, and coronary artery disease. Additionally, a Parkinson’s disease gene involved in dopamine regulation was also found to be associated with PTSD. “Similar to other mental disorders, the genetic contribution to PTSD correlates with that for many other traits. 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,” Karestan Koenen, a senior author of the study and associate member of the Stanley Center for Psychiatric Research at MIT and Harvard University, and a professor of psychiatric epidemiology in the Harvard T.H. Chan School of Public Health, said in the release.

Koenen adds: “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. 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.”