Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach

Kaitlin E Bountress¹, Leslie A Brick², Christina Sheerin³, Andrew Grotzinger⁴, Daniel Bustamante⁵, Sage E Hawn⁶, Nathan Gillespie³, Robert M Kirkpatrick³, Henry Kranzler⁷, Rajendra Morey⁸, Howard J Edenberg⁹, Adam X Maihofer¹⁰, Seth Disner¹¹, Allison Ashley-Koch¹², Roseann Peterson³, Adriana Lori¹³, Dan J Stein¹⁴, Nathan Kimbrel¹⁵, Caroline Nievergelt¹⁰, Ole A Andreassen¹⁶, Jurjen Luykx¹⁷, Arash Javanbakht¹⁸, Nagy A Youssef¹⁹; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group; Ananda B Amstadter³

Affiliations

¹ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA. Electronic address: kaitlin.bountress@vcuhealth.org.
² Department of Psychiatry and Human Behavior, Quantitative Sciences Program, Alpert Medical School at Brown University, USA.
³ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA.
⁴ Behavioral, Psychiatric, and Statistical Genetics, Institute for Behavior Genetics, University of Colorado Boulder, USA.
⁵ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA; Integrative Life Sciences Doctoral Program, Virginia Commonwealth University, USA.
⁶ National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA.
⁷ University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
⁸ VA Mid-Atlantic Mental Illness Research Education and Clinical Center, Durham VAMC, Durham, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
⁹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
¹⁰ Department of Psychiatry, University of California, San Diego, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
¹¹ Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA.
¹² Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
¹³ Department of Psychiatry and Behavioral Sciences, Emory University, USA.
¹⁴ Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁵ VA Mid-Atlantic Mental Illness Research Education and Clinical Center, Durham VAMC, Durham, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
¹⁶ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁷ School for Mental Health and Neuroscience, Maastricht University Medical Centre, Department of Psychiatry and Neuropsychology Maastricht, The Netherlands; UMC Utrecht Brain Center, University Medical Center Utrecht, Department of Psychiatry Utrecht, University, Utrecht, The Netherlands; Outpatient second opinion clinic, GGNet Mental Health, Warnsveld, The Netherlands.
¹⁸ Stress, Trauma, and Anxiety Research Clinic (STARC), Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.
¹⁹ Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA.

PMID: 35367939
PMCID: PMC9018560
DOI: 10.1016/j.drugalcdep.2022.109430

Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach

Kaitlin E Bountress et al. Drug Alcohol Depend. 2022.

. 2022 May 1:234:109430.

doi: 10.1016/j.drugalcdep.2022.109430. Epub 2022 Mar 28.

Authors

Affiliations

¹ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA. Electronic address: kaitlin.bountress@vcuhealth.org.
² Department of Psychiatry and Human Behavior, Quantitative Sciences Program, Alpert Medical School at Brown University, USA.
³ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA.
⁴ Behavioral, Psychiatric, and Statistical Genetics, Institute for Behavior Genetics, University of Colorado Boulder, USA.
⁵ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA; Integrative Life Sciences Doctoral Program, Virginia Commonwealth University, USA.
⁶ National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA.
⁷ University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
⁸ VA Mid-Atlantic Mental Illness Research Education and Clinical Center, Durham VAMC, Durham, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
⁹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
¹⁰ Department of Psychiatry, University of California, San Diego, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
¹¹ Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA.
¹² Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
¹³ Department of Psychiatry and Behavioral Sciences, Emory University, USA.
¹⁴ Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁵ VA Mid-Atlantic Mental Illness Research Education and Clinical Center, Durham VAMC, Durham, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
¹⁶ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁷ School for Mental Health and Neuroscience, Maastricht University Medical Centre, Department of Psychiatry and Neuropsychology Maastricht, The Netherlands; UMC Utrecht Brain Center, University Medical Center Utrecht, Department of Psychiatry Utrecht, University, Utrecht, The Netherlands; Outpatient second opinion clinic, GGNet Mental Health, Warnsveld, The Netherlands.
¹⁸ Stress, Trauma, and Anxiety Research Clinic (STARC), Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.
¹⁹ Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA.

PMID: 35367939
PMCID: PMC9018560
DOI: 10.1016/j.drugalcdep.2022.109430

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.

Keywords: Alcohol use; Alcohol use disorder; Genetic architecture; Genetic correlation; Genomic structural equation modeling (genomicSEM); Posttraumatic stress disorder (PTSD).

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Figures

**Figure 1.**
Depiction of Tested Models. Notes: Standardized loadings and correlations are depicted; *p<.05, **p<.01, ***p<.001. Line textures and thicknesses vary as an indictor of which items load on which factor.

See this image and copyright information in PMC

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Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach

Affiliations

Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous