Recent Genetics and Epigenetics Approaches to PTSD

Abstract

A substantial portion of the variance explaining differential risk responses to trauma exposure may be explained by differential inherited and acquired genetic and epigenetic risk. This biological risk is complemented by alterations in the functional regulation of genes via environmentally induced epigenetic changes, including prior childhood and adult trauma exposure. This review will cover recent findings from large-scale genome-wide association studies as well as newer epigenome-wide studies. We will also discuss future "phenome-wide" studies utilizing electronic medical records as well as targeted genetic studies focusing on mechanistic ways in which specific genetic or epigenetic alterations regulate the biological risk for PTSD.

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…The investigation of the genetic basis for PTSD remains in its early stages, in part owing to the highly polygenic nature of the genetic risk, the heterogeneity of trauma exposures and the heterogeneity among methodologies employed, which has made meta-analysis difficult 4, 171 . The basic design of genetic studies within PTSD is to apply a case–control approach, in which alleles of interest are tested for their association with individuals in which PTsD has developed compared with trauma-exposed controls.…”

Psychophysiological approaches to understanding the impact of trauma exposure

“…Population genetics (twin, family, and adoption studies) has established the substantial heritability of PTSD, although an estimated 30%-40% heritability of PTSD is similar to that determined for many other mental disorders (Banerjee, Morrison, & Ressler, 2017;Daskalaskis, Rijal, King, Huchkins, & Ressler, 2019). Molecular genetics complement population genetics by delineating gene pathways associated with PTSD.…”

“…However, current evidence also highlights common gene configurations in facilitating PTSD risk/resilience. Additionally, the complex interaction of genetic predisposition and epigenetic modifications upon environmental adversity affects psychophysiological systems (e.g., Banerjee et al, 2017;Daskalaskis et al, 2019;Jakovljevic, 2019;Nievergelt et al, 2019), rendering firm conclusions premature.…”

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

“…Several GWASs of PTSD have been conducted recently (Almli et al, ; Ashley‐Koch et al, ; Daskalakis, Rijal, King, Huckins, & Ressler, ; Duncan et al, ; Guffanti et al, ; Logue et al, ; Nievergelt et al, ; Nievergelt et al, ; Stein et al, ; Xie et al, ), including in veteran populations (Ashley‐Koch et al, ). The sample sizes in GWASs to date have varied, with the largest being a meta‐analysis of 20,730 persons (Duncan et al, ).…”

“…Several GWASs of PTSD have been conducted recently (Almli et al, 2015;Ashley-Koch et al, 2015;Daskalakis, Rijal et al, 2015). The sample sizes in GWASs to date have varied, with the largest being a meta-analysis of 20,730 persons (Duncan et al, 2018).…”