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.
N1 - Funding Information:
The effort of co-authors was supported by NIAAA ( 1K01 AA028058 [KB], 1K01 AA025692 [CS]), NIMH ( MH020030–21A1 [DB], R01MH120219 [ADG], R01 MH111671 [RAM], K01MH113848 [REP], R01MH124847–01 [CN], T32MH019836 [SEH), NIA ( RF1AG073593 [ADG]), U.S. Department of Veterans Affairs Rehabilitation Research and Development Service ( IK2RX002922 [SGD]), and The Brain & Behavior Research Foundation NARSAD grant 28632P&S Fund [REP]. Financial support for the PTSD PGC was provided by the Cohen Veterans Bioscience, Stanley Center for Psychiatric Research at the Broad Institute, One Mind , and the National Institute of Mental Health ( R01MH106595 ). The PGC-SUD Working Group receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532 . Statistical analyses for the PGC were carried out on the Genetic Cluster Computer ( http://www.geneticcluster.org ) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003 ), along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam . Dr. Youssef received research support from Department of Veterans Affairs (VA), Department of Defense (DOD), and research support but not salary support from PCORI , MECTA Corporation , Vistagen , and Merck . The opinions in this paper are the authors and do not represent the views of the VA, DOD, the National Institutes of Health, or the United States Government.
Funding Information:
The effort of co-authors was supported by NIAAA (1K01 AA028058 [KB], 1K01 AA025692[CS]), NIMH (MH020030?21A1 [DB], R01MH120219[ADG], R01 MH111671 [RAM], K01MH113848 [REP], R01MH124847?01[CN], T32MH019836[SEH), NIA (RF1AG073593[ADG]), U.S. Department of Veterans Affairs Rehabilitation Research and Development Service (IK2RX002922[SGD]), and The Brain & Behavior Research Foundation NARSAD grant 28632P&S Fund [REP]. Financial support for the PTSD PGC was provided by the Cohen Veterans Bioscience, Stanley Center for Psychiatric Research at the Broad Institute, One Mind, and the National Institute of Mental Health (R01MH106595). The PGC-SUD Working Group receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003), along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Dr. Youssef received research support from Department of Veterans Affairs (VA), Department of Defense (DOD), and research support but not salary support from PCORI, MECTA Corporation, Vistagen, and Merck. The opinions in this paper are the authors and do not represent the views of the VA, DOD, the National Institutes of Health, or the United States Government.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/5/1
Y1 - 2022/5/1
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.
KW - Alcohol use
KW - Alcohol use disorder
KW - Genetic architecture
KW - Genetic correlation
KW - Genomic structural equation modeling (genomicSEM)
KW - Posttraumatic stress disorder (PTSD)
UR - http://www.scopus.com/inward/record.url?scp=85127252785&partnerID=8YFLogxK
U2 - 10.1016/j.drugalcdep.2022.109430
DO - 10.1016/j.drugalcdep.2022.109430
M3 - Article
AN - SCOPUS:85127252785
SN - 0376-8716
VL - 234
SP - 1
EP - 8
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
M1 - 109430
ER -