Researchers identified a novel polygenic expression aggregate among World Trade Center responders with PTSD, but not in control responders without PTSD.
The researchers conducted a transcriptome-wide RNA sequencing study of whole blood in 201 World Trade Center responders who never had PTSD, 81 who currently reported PTSD, and 42 who reported having it in the past.
The researchers randomly divided the responders with current PTSD and those who never had PTSD into a discovery cohort (n = 195) and a replication cohort (n = 87).
They created a polygenic expression score using differentially expressed genes in a pathway analysis. The discovery cohort comprised 448 differentially expressed genes. In the replication cohort, 99 of those genes remained significant, according to the findings. One of those genes, FKBP5, was upregulated in individuals with current PTSD regardless of genotype, according to the findings.
The researchers observed glucocorticoid receptor signaling and immunity-related pathways, but these did not survive false discovery rate correction.
Thirty differentially expressed genes were aggregated to create a polygenic expression score, which yielded a sensitivity of 0.917 and a specificity of 0.508 in identifying individuals reporting current PTSD in the replication cohort.
Among individuals reporting current or past PTSD, the polygenic scores were similar. In addition, both current and past PTSD participants experienced higher scores than participants who never had PTSD.
“Together with the pathway analysis results, these findings point to [hypothalamic-pituitary-adrenal]-axis and immune dysregulation as key biological processes underpinning PTSD,” the researchers concluded. “A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.” – by Rob Volansky
Disclosure: The authors report no relevant financial disclosures.