Genetic approaches for the study of PTSD: Advances and challenges

Abstract

Post-traumatic stress disorder (PTSD) is a highly debilitating stress and anxiety-related disorder that occurs in response to specific trauma or abuse. Genetic risk factors may account for up to 30–40% of the heritability of PTSD. Understanding the gene pathways that are associated with PTSD, and how those genes interact with the fear and stress circuitry to mediate risk and resilience for PTSD will enable the development of targeted therapies to prevent the occurrence of or decrease the severity of this complex multi-gene disorder. This review will summarize recent research on genetic approaches to understanding PTSD risk and resilience in human populations, including candidate genes and their epigenetic modifications, genome-wide association studies and neural imaging genetics approaches. Despite challenges faced within this field of study such as inconsistent results and replications, genetic approaches still offer exciting opportunities for the identification and development of novel therapeutic targets and therapies in the future.

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.…”

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.…”

“…Only a modest number (and mostly unreplicated) PTSD risk loci have been identified to date (Almli et al, 2015;Ashley-Koch et al, 2015;Banerjee et al, 2017;Duncan et al, 2018;Nievergelt et al, 2018;Sheerin et al, 2017;Stein et al, 2016). Our MVP-based combatexposed, 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).…”