Examining the genomes of more than 250,000 “Million Veteran Program” participants, the researchers identified genetic ties between post-traumatic stress disorder (PTSD) and anxiety and depressive disorders. The study findings were published in Nature Genetics.

The researchers conducted genome-wide association studies of PTSD in military veterans of the United States to explore the genetic association with 2 common comorbidities, depression and anxiety. They also examined brain regions affected, all with an eye toward aiding research into possible drug targets.

The researchers used biobanks within the US Veterans Affairs Million Veteran Program. They included PTSD phenotypic definitions and PTSD subdomains. They used genomic structural equation modeling to determine genetic relationships between PTSD and clinically comorbid phenotypes: major depressive disorder, anxiety, and neuroticism.


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The researchers found a genetic overlap in PTSD symptoms. Several genes were identified across the PTSD phenotype. The gene MAD1L1, which is also tied to schizophrenia and bipolar disorder, was repeatedly identified in participants.

The researchers do not know if PTSD differs by trauma type or developmental timing. Inquiry into common genetic variants was limited.

Although the association studies and hypotheses provide interesting clues, the researchers concluded, “Many other functional genomics tools can, and should, be brought to bear on the study of PTSD, expanding the scope of inquiry to encompass a holistic, integrative functional genomic analysis of this common, serious and yet still poorly understood and inadequately treated neuropsychiatric disorder.”

Disclosure: Some study authors declared affiliations with industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Stein MB, Levey DF, Cheng Z, et al; Department of Veterans Affairs Cooperative Studies Program (no. 575B); VA Million Veteran Program. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nat Genet. 2021;53(2):174-184. doi:10.1038/s41588-020-00767-x