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Posttraumatic stress disorder: from gene discovery to disease biology

Published online by Cambridge University Press:  15 February 2021

Renato Polimanti Open the ORCID record for Renato Polimanti [Opens in a new window]  and
Frank R. Wendt
Renato Polimanti*
Affiliation:
Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA Veterans Administration Connecticut Healthcare System, West Haven, CT, USA
Frank R. Wendt
Affiliation:
Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA Veterans Administration Connecticut Healthcare System, West Haven, CT, USA
*
Author for correspondence: Renato Polimanti, E-mail: [email protected]
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Abstract

Posttraumatic stress disorder (PTSD) is a complex mental disorder afflicting approximately 7% of the population. The diverse number of traumatic events and the wide array of symptom combinations leading to PTSD diagnosis contribute substantial heterogeneity to studies of the disorder. Genomic and complimentary-omic investigations have rapidly increased our understanding of the heritable risk for PTSD. In this review, we emphasize the contributions of genome-wide association, epigenome-wide association, transcriptomic, and neuroimaging studies to our understanding of PTSD etiology. We also discuss the shared risk between PTSD and other complex traits derived from studies of causal inference, co-expression, and brain morphological similarities. The investigations completed so far converge on stark contrasts in PTSD risk between sexes, partially attributed to sex-specific prevalence of traumatic experiences with high conditional risk of PTSD. To further understand PTSD biology, future studies should focus on detecting risk for PTSD while accounting for substantial cohort-level heterogeneity (e.g. civilian v. combat-exposed PTSD cases or PTSD risk among cases exposed to specific traumas), expanding ancestral diversity among study cohorts, and remaining cognizant of how these data influence social stigma associated with certain traumatic events among underrepresented minorities and/or high-risk populations.

Keywords

EWASGWASneuroimagingposttraumatic stress disorder (PTSD)transcriptomics
Type
Invited Review
Information
Psychological Medicine , Volume 51 , Special Issue 13: Updates on the Genetics of Major Psychiatric Disorders by Early Career Investigators from the Psychiatric Genomics Consortium , October 2021 , pp. 2178 - 2188
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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