1. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
- Author
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Mihaela Aslan, John Concato, Matthew J. Girgenti, Kelly Cho, Yuk-Lam Ho, Hongyu Zhao, Murray B. Stein, Krishnan Radhakrishnan, Ronald S. Duman, Zhongshan Cheng, Gita A. Pathak, Joel Gelernter, Daniel F. Levey, Renato Polimanti, VA Million Veteran Program, Daniel C Posner, Frank R. Wendt, Kelly M. Harrington, and Rachel Quaden
- 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 - 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.
- Published
- 2021