The impact of trauma on a person’s quality of life can be significant, with symptoms such as intrusive thoughts and mood changes affecting those with posttraumatic stress disorder (PTSD). Although only about 6 percent of trauma survivors develop PTSD, the neurobiology of the disorder is not fully understood. A recent genetic study of over 1.2 million individuals has identified 95 loci in the genome that are associated with the risk of developing PTSD, including 80 that were previously unknown. These findings shed new light on the genetic factors involved in the development of PTSD.
In posttraumatic stress disorder (PTSD), intrusive thoughts, changes in mood, and other symp rnrnreveals new insights into the genetic basis of PTSD. The study’s findings suggest that genetics play a significant role in the development of PTSD and could potentially lead to better understanding and treatment of the disorder. These findings are a significant step forward in our understanding of PTSD and could pave the way for more effective interventions and therapies for those affected by the disorder. This research opens up new possibilities for identifying individuals at risk for PTSD and developing personalized treatment approaches.identified 43 genes associated with causing PTSD. The study was published in Nature Genetics.
Caroline Nievergelt, a professor in the Department of Psychiatry at the University of California, San Diego, stated, “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.” Co-first author Adam Maihofer, a genetic epidemiologist in Nievergelt’s lab, also contributed to the study.
The findings confirm previously established that The genetic basis of PTSD has been explored, offering numerous new areas for further research into potential prevention and treatment methods in the future.
“It’s remarkable to see the significant rise in genetic locations as sample size increases, similar to what we observe for other disorders,” said Karestan Koenen, the senior author of the study. Koenen is a member of the Broad Institute of MIT and Harvard, and an investigator with the Stanley Center for Psychiatric Research at Broad. She also leads the Stanley Center’s Biology of Trauma Initiative and the Global Neuropsychiatric Genomics Initiative, as well as being a professor of psychiatric epidemiology at Harvard.The T. H. Chan School of Public Health has reached a significant step in PTSD genetics.
Previous research on twins and genetics, which included a study in 2017 and an expanded one in 2019 by the same team, revealed that PTSD is influenced by genetics and multiple genes play a role in the condition.
However, these studies identified different genetic loci across datasets, and many had difficulty in distinguishing loci specifically linked to PTSD risk from those also associated with depression and cardiovascular disease. Additionally, The focus of research on trauma and PTSD has primarily been on individuals of European ancestry, despite the fact that there is a disproportionately high prevalence of trauma and PTSD among people of African, Native American, and Latin American ancestry in the United States and globally.
For the new study, Nievergelt, Koenen, and other researchers from the PGC gathered data from 88 different genome-wide association studies. These studies use genetic data from large groups of people to identify connections between specific regions of the genome and the likelihood of developing a particular condition or trait. The dataset included information on the risk of developing PTSD from over 1.2 million individuals of European ancestry.An analysis of the data showed that there were 95 regions strongly linked to PTSD, including 80 that were not previously known. Forty-three genes were found to be involved in causing PTSD, some of which impact neurons, neurotransmitters, ion channels, synapses, and the endocrine and immune systems. The study included individuals with European ancestry (approximately 140,000 with PTSD), African ancestry (approximately 50,000 with PTSD), and Native American ancestry (approximately 7,000 with PTSD).PTSD has many genetic similarities to depression and has several specific genetic areas related to PTSD. Previous research suggested that PTSD is more common in women than in men, but the researchers did not find evidence to support this in their data. They specifically looked at the X chromosome, which previous studies did not consider, and identified five genetic spots linked to PTSD. However, they noted that these changes on the X chromosome would have similar effects in both males and females. To further explore how genetics related to PTSD impact the brain, the team analyzed gene expression data and discovered that the cerebellum, a part of the brain that controls movement and balance, may be involved.The study discovered that specific genes were associated with PTSD, confirming previous knowledge about the disorder. The research team also identified new brain regions involved in PTSD, such as the interneurons, which connect motor and sensory neurons. Further research could explore how these genes and brain regions influence PTSD symptoms and behaviors. Kerry Ressler commented, “This is the first step towards understanding the genetic basis of PTSD, validating existing knowledge while also uncovering new targets and mechanisms for treatment.”co-leader of the PGC — PTSD working group, chief scientific officer at McLean Hospital, and Professor of Psychiatry at Harvard Medical School. “These findings represent a crucial initial phase in developing new strategies for treating PTSD.”
Consistent with previous research, Nievergelt, Koenen, and their team also determined that polygenic scores — a calculation of an individual’s genetic predisposition to a specific condition based on millions of single-letter changes in their DNA — for PTSD risk are not universally applicable across different populations. The scientists emphasize the significance of further broadening the research to address this variation.The depth and diversity of populations included in future studies of PTSD should be expanded. “We know that trauma and PTSD disproportionately affects under-resourced populations globally, particularly African ancestry populations,” said Koenen. “Our next steps will focus on addressing that inequity through partnerships with African scientists to make sure research in PTSD genetics benefits everyone equally.”
Funding:
This work was supported by the National Institute of Mental Health, Cohen Veterans Bioscience, and the Stanley Center for Psychiatric Research at the Broad Institute.
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