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

Kaitlin E Bountress; Leslie A Brick; Christina Sheerin; Andrew Grotzinger; Daniel Bustamante; Sage E Hawn; Nathan Gillespie; Robert M Kirkpatrick; Henry Kranzler; Rajendra Morey; Howard J Edenberg; Adam X Maihofer; Seth Disner; Allison Ashley-Koch; Roseann Peterson; Adriana Lori; Dan J Stein; Nathan Kimbrel; Caroline Nievergelt; Ole A Andreassen; Jurjen Luykx; Arash Javanbakht; Nagy A Youssef; Ananda B Amstadter; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup

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^*, Leslie A Brick, Christina Sheerin, Andrew Grotzinger, Daniel Bustamante, Sage E Hawn, Nathan Gillespie, Robert M Kirkpatrick, Henry Kranzler, Rajendra Morey, Howard J Edenberg, Adam X Maihofer, Seth Disner, Allison Ashley-Koch, Roseann Peterson, Adriana Lori, Dan J Stein, Nathan Kimbrel, Caroline Nievergelt, Ole A AndreassenJurjen Luykx, Arash Javanbakht, Nagy A Youssef, Ananda B Amstadter, Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Article number	109430
Journal	Drug and Alcohol Dependence
Volume	234
Early online date	28 Mar 2022
DOIs	https://doi.org/10.1016/j.drugalcdep.2022.109430
Publication status	Published - May 2022

Access to Document

10.1016/j.drugalcdep.2022.109430Licence: Free access - publisher

Cite this

Bountress, K. E., Brick, L. A., Sheerin, C., Grotzinger, A., Bustamante, D., Hawn, S. E., Gillespie, N., Kirkpatrick, R. M., Kranzler, H., Morey, R., Edenberg, H. J., Maihofer, A. X., Disner, S., Ashley-Koch, A., Peterson, R., Lori, A., Stein, D. J., Kimbrel, N., Nievergelt, C., ... Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup (2022). Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach. Drug and Alcohol Dependence, 234, Article 109430. https://doi.org/10.1016/j.drugalcdep.2022.109430

@article{5aab9f1b310d476794646f094815de77,

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

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.",

author = "Bountress, {Kaitlin E} and Brick, {Leslie A} and Christina Sheerin and Andrew Grotzinger and Daniel Bustamante and Hawn, {Sage E} and Nathan Gillespie and Kirkpatrick, {Robert M} and Henry Kranzler and Rajendra Morey and Edenberg, {Howard J} and Maihofer, {Adam X} and Seth Disner and Allison Ashley-Koch and Roseann Peterson and Adriana Lori and Stein, {Dan J} and Nathan Kimbrel and Caroline Nievergelt and Andreassen, {Ole A} and Jurjen Luykx and Arash Javanbakht and Youssef, {Nagy A} and Amstadter, {Ananda B} and {Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup}",

year = "2022",

month = may,

doi = "10.1016/j.drugalcdep.2022.109430",

language = "English",

volume = "234",

journal = "Drug and Alcohol Dependence",

issn = "0376-8716",

publisher = "Elsevier Ireland Ltd",

}

Bountress, KE, Brick, LA, Sheerin, C, Grotzinger, A, Bustamante, D, Hawn, SE, Gillespie, N, Kirkpatrick, RM, Kranzler, H, Morey, R, Edenberg, HJ, Maihofer, AX, Disner, S, Ashley-Koch, A, Peterson, R, Lori, A, Stein, DJ, Kimbrel, N, Nievergelt, C, Andreassen, OA, Luykx, J, Javanbakht, A, Youssef, NA, Amstadter, AB & Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup 2022, 'Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach', Drug and Alcohol Dependence, vol. 234, 109430. https://doi.org/10.1016/j.drugalcdep.2022.109430

TY - JOUR

T1 - Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD

T2 - A genomic structural equation modelling approach

AU - Bountress, Kaitlin E

AU - Brick, Leslie A

AU - Sheerin, Christina

AU - Grotzinger, Andrew

AU - Bustamante, Daniel

AU - Hawn, Sage E

AU - Gillespie, Nathan

AU - Kirkpatrick, Robert M

AU - Kranzler, Henry

AU - Morey, Rajendra

AU - Edenberg, Howard J

AU - Maihofer, Adam X

AU - Disner, Seth

AU - Ashley-Koch, Allison

AU - Peterson, Roseann

AU - Lori, Adriana

AU - Stein, Dan J

AU - Kimbrel, Nathan

AU - Nievergelt, Caroline

AU - Andreassen, Ole A

AU - Luykx, Jurjen

AU - Javanbakht, Arash

AU - Youssef, Nagy A

AU - Amstadter, Ananda B

AU - Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working GroupGroup

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.drugalcdep.2022.109430

DO - 10.1016/j.drugalcdep.2022.109430

M3 - Article

C2 - 35367939

SN - 0376-8716

VL - 234

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

M1 - 109430

ER -