In a collaborative effort, researchers worldwide have produced an intricate map delineating the genetic factors associated with post-traumatic stress disorder (PTSD).
The largest genetic study ever conducted on PTSD has unveiled 95 regions in the genome linked to the condition, including 80 previously unidentified areas. This comprehensive genetic dataset holds the potential to pave the way for novel PTSD therapies, according to scientists.
PTSD is a psychiatric disorder that can emerge following exposure to traumatic events, often persisting as a chronic condition. Chronic PTSD affects approximately 10% of the general population and even higher proportions in high-risk groups such as combat veterans and survivors of assault.
Prior genetic investigations, primarily focused on identical twins, underscored the significant genetic influence on PTSD susceptibility, akin to conditions like addiction and depression. However, these studies provided only a fragmentary view of the intricate genetic landscape underlying PTSD, which potentially involves hundreds of genes.
Published in the journal Nature Genetics on April 18, the new study leveraged data from over 1 million individuals, comprising approximately 13% with PTSD and 87% without. Employing a genome-wide association study (GWAS), researchers scrutinized genetic data from individuals both afflicted and unaffected by the disorder, pinpointing genetic markers associated with PTSD onset.
Given the vast variability in genetic makeup among individuals, large-scale studies encompassing diverse populations are crucial to identify common genetic markers. Dr. Kerry Ressler, chief scientific officer and chair in psychiatry at McLean Hospital, emphasized the significance of expanding the study’s scope to include over a million participants, including non-European ancestries.
The study identified 95 genetic risk markers, 15 of which corroborated previous findings. Many of these markers exhibited associations with both PTSD and depression, while some were specific to PTSD. Additionally, the study highlighted 43 genes in proximity to these markers, presenting potential targets for treatment interventions.
Noteworthy genes implicated in stress and fear responses, such as CRHR1 and FOXP2, were identified as potential contributors to PTSD. Moreover, the study identified multiple proteins serving as potential biomarkers for assessing an individual’s susceptibility to PTSD.
Furthermore, the study explored the role of the X chromosome in PTSD susceptibility, shedding light on the estrogen receptor gene’s proximity to a risk marker. Given the higher prevalence of PTSD among women, further investigation into estrogen’s role may elucidate sex-specific differences in the disorder.
Carrie Bearden, a professor of neuroscience and human behavior at UCLA, hailed the study as a significant milestone in unraveling the genetic underpinnings and biological mechanisms of PTSD. She emphasized the study’s ability to discern shared and disorder-specific genetic risk loci and their connections to underlying biological systems.
Looking ahead, the consortium aims to incorporate more ethnically diverse populations, particularly from Africa, to address the substantial trauma burden prevalent in war-torn regions. Additionally, they seek to integrate genetic data with brain tissue gene activity data to pinpoint regions of heightened gene activity and potential treatment targets.