A research team, headed by scientists from the University of California, San Diego, Veterans Affairs San Diego Healthcare System (VASDHS), Yale University, and West Haven VA, has found 18 specific, fixed positions on chromosomes (called loci) that seem to be linked to post-traumatic stress disorder (PTSD).
Murray Stein, MD, MPH. Image Credit: University of California, San Diego.
The researchers made this discovery after examining the genomes of over one-quarter of a million military veterans.
These latest findings confirm the fundamental biology of PTSD, its association with comorbid depressive and anxiety disorders, and offer promising new targets for treatment, wrote the study authors in the online issue of the Nature Genetics journal on January 28th, 2021.
We’re very intrigued by the findings of this study, for example, as they pertain to the genetic relationships between different kinds of PTSD symptoms. It also shows the huge value of the Million Veteran Program in facilitating research important to the care of our military veterans.”
Murray Stein, MD, MPH, Study Co-Principal Investigator and Psychiatrist, Veterans Affairs San Diego Healthcare System
Dr Stein is also the Distinguished Professor of Psychiatry and Family Medicine and Public Health at UC San Diego School of Medicine.
The researchers performed genome-wide association studies (GWAS) of over 250,000 individuals of African and European ancestry who took part in the Million Veteran Program. In GWAS, markers are quickly scanned across comprehensive sets of genomes, or DNA¸ of several people to detect genetic changes linked to a specific disease.
The Million Veteran Program was introduced in 2011 and this research effort was sponsored by the U.S. Veteran Affairs to understand how lifestyle, genes, and military exposures influence both health and illness. Over 825,000 U.S. veterans took part in the program.
The team surveyed the electronic health records of the veterans for diagnosed cases of PTSD as well as for quantitative symptoms, like physical reactions to reminders of traumatic events or severe emotional distress, recurrent intrusive memories of traumatic events, difficulty in sleeping, and self-destructive behaviors.
PTSD is known to be a major mental disorder that can manifest following exposure to severe, life-threatening stress. It has been estimated that traumatic events are experienced by half to over three-quarters of Americans over their lifetimes; however, the majority of the individuals do not develop PTSD disorder.
The lifetime prevalence for PTSD is around 7% (but relatively higher among veterans), indicating that individuals have different levels of resilience to vulnerability and stress to the disorder.
It has been known for a long time that vulnerability to PTSD is heritable. Similar to other mental disorders, PTSD is a highly complex phenotype, or a class of observable traits, affected by numerous genes. Undoubtedly, present diagnostic guidelines enable up to 163,120 exclusive conformations of symptoms for the PTSD disorder.
The research work directly compared the continuous, symptom-based phenotypes of PTSD with the heritability of diagnostic PTSD cases. Although PTSD symptoms are highly diverse, their genetic overlap is also high—a crucial insight into the fundamental biology of the condition.
The investigators detected numerous genes that were constantly implicated in varied phenotypes of PTSD, suggesting that both that the genes were crucial players in the development of PTSD and that they might be appropriate targets for therapeutic medications.
These findings give us new insights into the biological basis of PTSD, and point to some possible next steps for testing new treatments.”
Joel Gelernter, MD, Study Co-Principal Investigator and Professor of Psychiatry, Genetics and Neuroscience, Yale School of Medicine, VA Connecticut Healthcare System
Stein, M. B., et al. (2021) Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics. doi.org/10.1038/s41588-020-00767-x.