Genetic risk mechanisms of posttraumatic stress disorder in the human brain
Rahul A. Bharadwaj, Andrew E. Jaffe, Qiang Chen, Amy Deep-Soboslay, Aaron L. Goldman, Michelle I. Mighdoll, John A. Cotoia, Anna C. Brandtjen, JooHeon Shin, Thomas M. Hyde, Venkata S. Mattay, Daniel R. Weinberger and Joel E. Kleinman
Version of Record online: 24 OCT 2016 | DOI: 10.1002/jnr.23957
PTSD genetic risk mechanisms in the human brain. Legend: The graphical overview of our research findings is a proven example of how genetic risk mechanisms potentially operate through multiple modalities including gene expression (RNA sequencing), epigenetics (DNA methylation), and neurophysiology (fMRI) in the human brain. Using “risk” DNA biomarkers such as SNPs improves the tractability insofar as studies addressing plain case–control differences are confounded by substance abuse, treatment, and epiphenomena that are unknown in the absence of a tractable genetic sequence biomarker. To illustrate, we show associations for allelic variation at candidate PTSD “risk” SNP rs363276 (CC/CT/TT) where the risk allele “T” carriers show significant changes across multiple modalities. We present an approach of how we can map mechanisms associated with clinical risk that progress towards either “resilience to” or “risk of” developing PTSD in “normal” controls. Now that we have dissected these mechanisms in “normal” brains, the next step would include evaluating these findings in the brains of subjects diagnosed with PTSD where any differences in these associations can be attributable to PTSD disease phenomena, especially when a control psychiatric group such as “major depression” or “bipolar disorder” is included.