Newsletter SignupSearch


Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Biological Psychiatry 2022; 91(7): 626-636 revised 1 April 2022
Authored By:
Adam X. Maihofer, Karmel W. Choi, Jonathan R.I. Coleman et al.
Background Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.
Published in:
Biological Psychiatry

More Publications

September 9, 2022


Deep Learning for Daily Monitoring of Parkinson’s Disease Outside the Clinic Using Wearable Sensors

June 1, 2022

JAMA Network Open

Association of Posttraumatic Stress Disorder With Accelerated Cognitive Decline in Middle-aged Women

March 23, 2022

Journal of Neurotrauma

A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury

February 26, 2022

Translational Psychiatry

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

January 31, 2022

Biological Psychiatry

Noncoding RNAs: Stress, Glucocorticoids, and Posttraumatic Stress Disorder

December 1, 2021

Neurotrauma Reports

Neurotrauma Reports Special Collection: Null Hypothesis Initiative

Cohen Veterans Bioscience - Advancing Brain Health

Get the latest updates in TBI and PTSD research

Sign up for our newsletter to learn how we’re advancing solutions for brain trauma.

This field is for validation purposes and should be left unchanged.