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.

Systems Biology Sample Survey

The PGC-PTSD SysBio working group would like to conduct a large scale transcriptomics focused study of PTSD and related phenotypes. We are requesting information about datasets which have transcriptomic data only, but also datasets where transcriptomic data can be linked to genetic and/or DNA methylation data (for all and/or a subset of samples). The source of transcriptomic and related data could be any tissue or cell type. Please fill in the survey here:

Dr. Nikolaos Daskalakis, MD, PhD

Nikolaos P. Daskalakis, MD, PhD, is the director of the Neurogenomics and Translational Bioinformatics Laboratory at McLean Hospital and an assistant professor of psychiatry at Harvard Medical School. He is also an affiliate member of the Broad Institute, MIT Computer Science and Artificial Intelligence Laboratory, and the National Center for PTSD. He received his MD from University of Athens, his PhD in neuropsychopharmacology from Leiden University, and completed post-doctoral fellowships in clinical neuroendocrinology at Leiden University Medical Center and in molecular psychiatry/bioinformatics at Icahn School of Medicine.

Dr. Daskalakis focuses on the interaction between stress and the brain, conducting translational studies and following an integrative systems biology approach. His lab uses whole tissue and cell type specific transcriptomic and epigenomic profiling of brain and blood samples to identify gene networks associated with vulnerability and resilience to PTSD. Dr. Daskalakis co-leads the Systems Biology working group of the Psychiatric Genomics Consortium for PTSD. He is an editor for Brain Sciences and Frontiers (in Behavioral Neuroscience, Endocrinology, Neuroscience, and Psychiatry).

Alison Ashley-Koch, Ph.D.

Dr. Ashley-Koch is a Professor in the Duke Molecular Physiology Institute at Duke University Medical Center. She received her PhD in Genetics and Molecular Biology from Emory University and performed postdoctoral training at the Centers for Disease Control and Prevention and Duke University Medical Center. Dr. Ashley-Koch is a genetic epidemiologist whose primary goal is the identification of genetic and genomic risk factors that contribute to a variety of human phenotypes, with a focus on psychiatric traits. Dr. Ashley-Koch performs genetic and genomic analysis of PTSD in military cohorts, including the VA Mid-Atlantic MIRECC and the InTrust data sets. She is also a member of the PsychENCODE project, which uses state of the art molecular tools to characterize genetic regulatory elements in brain tissues and cells. Dr. Ashley-Koch is a co-leader of the PGC-PTSD gene expression working group.

Dr. Shareefa Dalvie, PhD

Dr. Dalvie, PhD, is a faculty member at the Department of Psychiatry & Mental Health at the University of Cape Town (UCT) in South Africa and co-heads the Psychiatric Neurogenetics group of the Brain-Behaviour Unit (BBU) at UCT. She completed her doctoral degree at the Division of Human Genetics at UCT and held a Brain-Behaviour Initiative (BBI) postdoctoral fellowship from the Department of Psychiatry & Mental Health. Dr Dalvie’s research interests include the genetic basis of trauma exposure in individuals with post-traumatic stress disorder (PTSD), network analysis for PTSD integrating “omic” layers, and gene-imaging analysis. Dr Dalvie is also a visiting scholar at the University of California, San Diego (UCSD) in the USA and co-leads the Systems Biology working group of the Psychiatric Genomics Consortium (PGC)-PTSD. She is also a Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) research fellow (Stanley Center for Psychiatric Research and Harvard T. H. Chan School of Public Health, USA).