The genetics and epigenetics of PTSD: overview, recent advances, and future directions

Abstract

This paper provides a brief summary and commentary on the growing literature and current developments related to the genetic underpinnings of posttraumatic stress disorder (PTSD). We first briefly provide an overview of the behavioral genetic literature on PTSD, followed by a short synopsis of the substantial candidate gene literature with a focus on genes that have been meta-analyzed. We then discuss the genome-wide association studies (GWAS) that have been conducted, followed by an introduction to other molecular platforms used in PTSD genomic studies, such as epigenetic and expression approaches. We close with a discussion of developments in the field that include the creation of the PTSD workgroup of the Psychiatric Genomics Consortium, statistical advances that can be applied to GWAS data to answer questions of heritability and genetic overlap across phenotypes, and bioinformatics techniques such as gene pathway analyses which will further advance our understanding of the etiology of PTSD.

Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

“…PTSD is thought to develop, in large part, as a function of gene by environment (i.e., GxE) interactions (Ressler, 2016; Sheerin et al, 2017), and the behavioral expression of certain genotypes is sensitive to influence from the social environment (Kim et al, 2011). Individual differences in perceptions of the social environment, such as adult attachment style, serve as critical mechanisms of stress recovery and the development of social bonds (Charuvastra & Cloitre, 2008), such that attachment may serve as an environmental moderator of OXTR effects.…”

Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B

“…The high prevalence of military veterans with combat exposure (see Table ), which is a strong risk factor for PTSD and other comorbidities including suicidality, provides motivation for the current study. Only a modest number (and mostly unreplicated) PTSD risk loci have been identified to date (Almli et al, ; Ashley‐Koch et al, ; Banerjee et al, ; Duncan et al, ; Nievergelt et al, ; Sheerin et al, ; Stein et al, ). Our MVP‐based combat‐exposed, genotyped sample, with >16,000 PTSD cases and >33,000 non‐PTSD controls, provides a strong foundation to conduct a GWAS.…”

“…The sample sizes in GWASs to date have varied, with the largest being a meta‐analysis of 20,730 persons (Duncan et al, ). Replication of primary risk loci for PTSD has been a challenge, presumably because of small sizes of discovery and replication samples (Banerjee, Morrison, & Ressler, ; Sheerin, Lind, Bountress, Nugent, & Amstadter, ).…”

“…Replication of primary risk loci for PTSD has been a challenge, presumably because of small sizes of discovery and replication samples (Banerjee, Morrison, & Ressler, 2017;Sheerin, Lind, Bountress, Nugent, & Amstadter, 2017).…”

Neuroepigenetics of Post-Traumatic Stress Disorder

“…While diagnosis of PTSD is based on behavioral symptom clusters that are most directly associated with brain function, epigenetic studies of PTSD in humans (detailed in these reviews 9,10 ) have been limited to peripheral tissues, such as blood, buccal tissue, and saliva. Very few studies have been conducted in postmortem human brain tissues of individuals with PTSD 11–14 , and none have explored epigenetic mechanisms.…”