ADVANCES IN PTSD GENOMICS 2023

Dr. Adam Maihofer from UCSD will provide the latest updates from the PGC-PTSD GWAS where gene-mapping strategies applied to 81 significant loci have identified hundreds of potentially associated genes. Due to LD patterns, this collection contains causal genes and non-causal genes in LD with them. To prioritize the most likely causal genes, they integrated other -omics data and functional information with GWAS results. They prioritized a set of 126 genes that are enriched across databases such as SynGO and provide important insights into the biology of PTSD. Genetic studies of PTSD are complicated by the complex interplay between environmental traumatic exposures and genetics. To model this in vitro, MD PhD candidate Carina Seah from Brennand/Huckins labs at Mount Sinai and Yale will present a study where GABAergic and glutamatergic neurons were generated from combat-exposed veterans with PTSD (n=20) and without (n=20), and then treated with hydrocortisone (HCort). To delve into the common genetic variants mediating stress response, they modeled a linear eQTL association using an interaction term between HCort exposure and genotype, finding eQTLs that replicate those associated with trauma exposure in the post-mortem brain. These eQTLs enrich in binding sites associated with stress response and suggest a role for common genetic variation mediating response to trauma in PTSD. Dr. Raj Morey from Duke University will present the latest results in PTSD neuroimaging genetics that have identified genetic markers of hippocampal and amygdala substructures, used multivariate methods to identify genetically informed brain networks and their associated genetic markers. They will also discuss PGC-PTSD Neuroimaging Workgroup analysis plan to apply multivariate methods to explore genetic markers of brain resting-state functional connectivity, canonical resting-state networks, and the differential effects of these genetic markers in trauma-exposed and PTSD populations. Dr. Alicia Smith from Emory University will present novel epigenetic results of a meta-analysis of 5077 participants from 23 military and civilian cohorts. They identify CpG sites associated with PTSD in the overall model as well as those associated in analyses stratified by trauma type, sex, and ancestry. They then leverage data from postmortem brain samples, in vivo models, GWAS, and genome-wide expression data to interpret and prioritize genes whose regulation differs in those with PTSD. Dr. Kerry Ressler from Harvard Medical School and McLean Hospital will serve as the Discussant to summarize and integrate the findings with a view toward future directions.