Abstract

Purpose: Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed. Basic procedures: We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes. Main findings: When we differentiated genetic factors for alcohol use and AUD we observed improved model fit relative to models with all alcohol-related indicators loading onto a single factor. The genetic correlations (rG) of PTSD were quite discrepant for the alcohol use and AUD factors. This was true when modeled as a three-correlated-factor model (PTSD-AUD rG:.36, p < .001; PTSD-alcohol use rG: −0.17, p < .001) and as a Bifactor model, in which the common and unique portions of alcohol phenotypes were pulled out into an AUD-specific factor (rG with PTSD:.40, p < .001), AU-specific factor (rG with PTSD: −0.57, p < .001), and a common alcohol factor (rG with PTSD:.16, NS). Principal conclusions: These results indicate the genetic architecture of alcohol use and AUD are differentially associated with PTSD. When the portions of variance unique to alcohol use and AUD are extracted, their genetic associations with PTSD vary substantially, suggesting different genetic architectures of alcohol phenotypes in people with PTSD.

Original languageEnglish
Article number109430
JournalDrug and Alcohol Dependence
Volume234
DOIs
StatePublished - 1 May 2022
Externally publishedYes

Funding

FundersFunder number
Dutch Brain Foundation
MECTA
U.S. Department of Veterans Affairs Rehabilitation Research and Development Service
National Institutes of Health
U.S. Department of Defense
National Institute of Mental HealthR01 MH111671, K01MH113848, R01MH120219, 21A1, MH020030–21A1, T32MH019836, R01MH124847–01, R01MH106595
National Institute on Drug AbuseMH109532
National Institute on Alcohol Abuse and Alcoholism1K01 AA025692, 1K01 AA028058
National Institute on AgingRF1AG073593
U.S. Department of Veterans AffairsIK2RX002922
Brain and Behavior Research Foundation28632P
Merck
Patient-Centered Outcomes Research Institute
Broad Institute
Cohen Veterans Bioscience
Vrije Universiteit Amsterdam
Nederlandse Organisatie voor Wetenschappelijk Onderzoek480-05-003

    Keywords

    • Alcohol use
    • Alcohol use disorder
    • Genetic architecture
    • Genetic correlation
    • Genomic structural equation modeling (genomicSEM)
    • Posttraumatic stress disorder (PTSD)

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