Group Leaders: Dr. Nikolaos Daskalakis, M.D. Ph.D., Dr. Shareefa Dalvie, Ph.D. and Alison Ashley-Koch Ph.D.
Reductionist unimodal techniques did not have substantial success in identifying causal mechanisms for PTSD. There is a need for a more integrated multimodal approach to study the complex interplay between biological and phenotypic constructs.
We aim to delineate complex processes underlying PTSD using a systems biology approach by integrating biological and phenotypic “layers”.
As of 2021, the Systems Biology workgroup has merged with the Gene Expression workgroup, whose goal is to identify the genes that are differentially expressed in controls and individuals with current PTSD. The full PGC- PTSD consortium will generate gene expression data on several thousand individuals, greatly improving power. This data set can be also used in conjunction with multiple other types of ‘omics data, including DNA methylation and genome wide genotype data. This will allow multiple cross-platform analyses to be performed. For example, we will have sufficient power to conduct eQTL analyses to identify genetic variants that can alter the level of expression of specific genes. Likewise, we will be able to identify DNA methylation patterns that may be giving rise to altered gene expression. Such joint analyses of multiple –omics datasets have been previously termed “genomic convergence” and have great potential to inform us about the genetic architecture of PTSD. The working group has several challenges to consider. First, multiple platforms have been used for gene expression analysis—Affymetrix arrays, Illumina arrays, and RNAseq. Combining these data into a single analysis will require the development of new methods. Further, so expression datasets will not have associated GWAS or methylation data, making it harder to correct for population structure and cell type composition of blood samples. The working group will use multiple approaches to address these challenges.