Elizabeth Ketema

Project Personnel, University of California, San Diego

1 active project

PGC-PTSD: Determining the Genomic Architecture of PTSD

Up to 50% of the variance determining who develops Post-traumatic Stress Disorder following a severe trauma may be genetic; however, most successful analyses to date suggest that risk arises from multiple common genetic variants of small effect size, and that…

Scientific Questions Being Studied

Up to 50% of the variance determining who develops Post-traumatic Stress Disorder following a severe trauma may be genetic; however, most successful analyses to date suggest that risk arises from multiple common genetic variants of small effect size, and that very large sample sizes will be needed for detection. The Psychiatric Genomics Consortium PTSD workgroup (PGC-PTSD) aims to uncover the genomic architecture of PTSD through large-scale, collaborative genome-wide association studies. Identifying the pathways underlying PTSD will lead to an improved neurobiological understanding, enhanced prevention, and improved treatment of this debilitating and prevalent syndrome.

Project Purpose(s)

  • Disease Focused Research (Post-Traumatic Stress Disorder)
  • Ancestry

Scientific Approaches

The purpose of this application is to facilitate meta-analyses of GWAS data for symptoms and diagnosis of PTSD. Currently our multi-ethnic data collection includes genotypes from 60 studies with a total N of over 200K combined cases and trauma-exposed controls (Nievergelt et al., 2019).

Our NIMH-funded study has 4 Aims: to increase sample size to reach the PGC goal of 100K cases for psychiatric disorders, create psychometrically optimized PTSD sub-phenotypes, conduct GWAS meta-analyses to detect novel common variants, and identify CNVs hypothesized to contribute to PTSD heritability through rare and low-frequency CNVs. Aim 1 will be supplemented by the contribution of diverse ancestry groups to ensure that advances in our genetic understanding of PTSD extend across ancestral backgrounds. Aim 3 is centered around the characterization of functional consequences of identified variants. We will use PRS to provide insights into relationships to other traits and advance causal inference.

Anticipated Findings

We hypothesize that with an increased sample size and deeper phenotype characterization, the PGC-PTSD will accelerate our current understanding of the genetic architecture of PTSD. Identifying the genetic pathways underlying PTSD will lead to improved neurobiological understanding, enhanced prevention, and improved treatment of this debilitating and prevalent syndrome.

Demographic Categories of Interest

  • Race / Ethnicity

Research Team

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