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Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
- Source :
- Nature genetics
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- We conducted genome-wide association analyses of over 250,000 participants of European (EUR) and African (AFR) ancestry from the Million Veteran Program using electronic health record-validated post-traumatic stress disorder (PTSD) diagnosis and quantitative symptom phenotypes. Applying genome-wide multiple testing correction, we identified three significant loci in European case-control analyses and 15 loci in quantitative symptom analyses. Genomic structural equation modeling indicated tight coherence of a PTSD symptom factor that shares genetic variance with a distinct internalizing (mood–anxiety–neuroticism) factor. Partitioned heritability indicated enrichment in several cortical and subcortical regions, and imputed genetically regulated gene expression in these regions was used to identify potential drug repositioning candidates. These results validate the biological coherence of the PTSD syndrome, inform its relationship to comorbid anxiety and depressive disorders and provide new considerations for treatment. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in individuals of European and African ancestry provide insights into its relationship with anxiety and depressive disorders and identify potential candidates for drug repositioning.
- Subjects :
- Linkage disequilibrium
Genome-wide association study
Biology
Polymorphism, Single Nucleotide
Linkage Disequilibrium
White People
Article
Structural equation modeling
Stress Disorders, Post-Traumatic
03 medical and health sciences
0302 clinical medicine
mental disorders
Genetics
medicine
Humans
Veterans
030304 developmental biology
0303 health sciences
Mental Disorders
Drug Repositioning
Traumatic stress
Case-control study
Heritability
Anxiety Disorders
United States
Black or African American
Case-Control Studies
Multiple comparisons problem
Anxiety
medicine.symptom
030217 neurology & neurosurgery
Genome-Wide Association Study
Clinical psychology
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....7ec4dcc433e9d5da79c629ecf619c9b4