Study identifies genetic roots of post-traumatic stress disorder

In post-traumatic stress disorder (PTSD), intrusive thoughts, mood changes, and other symptoms following a trauma can greatly affect a person’s quality of life. About 6 percent of people who experience trauma develop the disorder, but scientists don’t yet understand the neurobiology behind PTSD.

Now, a new genetic study of more than 1.2 million people has identified 95 loci, or locations in the genome, associated with PTSD risk, including 80 previously undiscovered loci. The study, conducted by the PTSD Working Group within the Psychiatric Genomics Consortium (PGC – PTSD) in conjunction with Cohen Veterans Bioscience, is the largest and most diverse of its kind and also identified 43 factors that appear to be associated with causing PTSD. Gene.The piece appears today in Nature Genetics.

Caroline Nievergelt, co-first author and corresponding author of the study, said that based on the largest study of the genetics of PTSD conducted to date, this finding provides strong confirmation that the heritability of PTSD is core features and highlights the complexity of genetic factors that contribute to PTSD. Adam Maihofer, a genetic epidemiologist in Nivergelt’s laboratory, is also co-first author.

These findings both confirm previously discovered genetic basis for post-traumatic stress disorder (PTSD) and provide a number of new targets for future research that may lead to new prevention and treatment strategies.

“What’s exciting is that as sample sizes for other diseases increase, we see exponential growth in loci,” said study senior author Karestan Koenen, a member of the Broad Institute of MIT and Harvard and a researcher at the Stanley Center. Koenen directs the Stanley Center’s Trauma Biology Program and Global Neuropsychiatric Genomics Initiative and is professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health. This is a milestone in the genetics of PTSD.

genetic roots

Previous twin and genetic studies, including a 2017 investigation by the same team and an expanded study in 2019, have shown that PTSD has a genetic component and that many genes contribute to the condition.

But these analyzes pointed to different genetic loci in the dataset, and many studies have struggled to distinguish genetic loci specific to PTSD risk from those also associated with conditions such as depression and cardiovascular disease. Genetic datasets have also historically focused on people of European ancestry, although the burden of trauma and post-traumatic stress disorder is disproportionately high among people of African, Native American, and Latino ancestry in the United States and globally.

For the new study, Nievergelt, Koenen and other researchers at the PGC collected data from 88 different genome-wide association studies, which use genetic data from large populations to look for associations between regions of the genome and the development of conditions or feature. In total, the dataset contains information on PTSD risk for more than 1.2 million individuals of European ancestry (including approximately 140,000 individuals with PTSD), approximately 50,000 individuals of African ancestry (including approximately 12,000 individuals with PTSD), and approximately 7,000 individuals of Native American ancestry. (About 2,000 people with PTSD).

A meta-analysis of the data revealed 95 loci strongly associated with PTSD, including 80 previously undiscovered loci. Forty-three genes appear to play a role in causing post-traumatic stress disorder (PTSD), including some that affect brain cells called neurons, brain chemicals called neurotransmitters, and ion channels (which allow ions to move in and out of cells) , the connections between neurons called synapses, and endocrine genes. Researchers found that PTSD shares many genetic features with depression, as well as several PTSD-specific loci.

Although previous studies have found a higher prevalence of PTSD in women than men, the researchers found no evidence of this in their data. They examined the X chromosome and found five loci associated with PTSD, something that earlier studies had not done. But they add that these changes on the X chromosome can have similar effects in men and women.

To delve deeper into how PTSD genetics affect the brain, the team looked at gene expression data and found that in addition to areas scientists have previously linked to PTSD, the cerebellum (the area of ​​the brain that controls movement and balance) may also be implicated in the disorder, such as Such as cortex and amygdala. In particular, the team found that interneurons, which connect motor and sensory neurons, are associated with post-traumatic stress disorder risk. Future research may help determine how key genes in these tissues and cells influence post-traumatic stress disorder (PTSD) symptoms and behaviors.

This is the first time we have studied the genetic architecture of post-traumatic stress disorder (PTSD), which both validates previous understanding of some of the key biology behind trauma-related disorders and points to exciting new targets and Mechanism, leader of the PGC-PTSD Working Group, chief scientific officer of McLean Hospital, and professor of psychiatry at Harvard Medical School. These data are an important first step in the next generation of new interventions for post-traumatic stress disorder (PTSD).

Consistent with previous research, Nievergelt, Koenen and their colleagues also found that polygenic scores, which calculate a person’s genetic chances of having a disease based on millions of single-letter changes in DNA, were used to understand PTSD risk, but This approach does not translate easily among the population. The researchers say this disparity highlights the importance of continuing to expand the depth and diversity of populations in future studies of PTSD.

“We know that trauma and post-traumatic stress disorder (PTSD) disproportionately affect under-resourced communities around the world, especially those of African ancestry,” Cornyn said. Our next focus is to address this inequity by working with African scientists to ensure that research into the genetics of PTSD reaches everyone equally.

refer to: Nievergelt CM, Maihofer AX, Atkinson EG, et al. Genome-wide association analysis identifies 95 risk loci and provides insights into the neurobiology of post-traumatic stress disorder. Nature Genetics. 2024.doi:10.1038/s41588-024-01707-9

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