Differences in Genetic Correlations between Posttraumatic Stress Disorder and Alcohol Use Disorder-Related Phenotypes Compared to Alcohol Consumption-Related Phenotypes

Background Posttraumatic Stress Disorder (PTSD) tends to co-occur with greater alcohol consumption as well as alcohol use disorder (AUD). However, it is unknown whether the same etiologic factors that underlie PTSD-AUD comorbidity also contribute to PTSD-alcohol consumption. Methods We used summary statistics from large-scale genome-wide association studies (GWAS) of European-ancestry (EA) and African-ancestry (AA) participants to estimate genetic correlations between PTSD (both the diagnosis and re-experiencing symptoms) and a range of alcohol consumption-related and AUD-related phenotypes (e.g., drinks per week, max drinks, consumption, AUD). Results In EAs, there were positive genetic correlations between PTSD phenotypes and AUD-related phenotypes (i.e., Alcohol Use Disorders Identification Test (AUDIT) problem score, maximum alcohol intake, AUD, and alcohol dependence) (rGs: .132-.533, all FDR adjusted p<.05). However, the genetic correlations between PTSD phenotypes and alcohol consumption -related phenotypes (i.e., drinks per week, AUDIT consumption score, AUDIT total score, and a combination of consumption and problems) were negatively associated or non-significant (rGs: -.417- -.042, FDR adjusted p: <.05-NS). For AAs, the direction of correlations was sometimes consistent and sometimes inconsistent with that in EAs, and the ranges were larger (rGs for AUD--related: -.275 -.266, FDR adjusted p: NS, alcohol consumption-related: .145-.699, FDR adjusted p: NS). Conclusions These findings illustrate that the genetic associations between consumption and problem alcohol phenotypes and PTSD differ in both strength and direction. Thus, the genetic factors that may lead someone to develop PTSD and consume large quantities of alcohol are not the same as those that lead someone to develop PTSD-AUD. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NA Not clinical trial ### Funding Statement The effort of co-authors was supported by NIAAA (1K01 AA028058 [KB], 1K01 AA025692[CS], P50AA022537[REP, BTW]), NIMH (NIMH K01MH113848 [REP], MH020030-21A1 [DB]), and The Brain & Behavior Research Foundation NARSAD grant 28632 P&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 (NIMH; 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. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study involves only openly available human data, which can be obtained from: Million Veterans Program, Psychiatric Genomics Consortium (PGC)-PTSD and SUD Workgroups, UK Biobank, GSCAN, and 23andMe I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced/generated in the present study are available upon reasonable request to the authors. However, individual summary statistic files that are referred to may only be obtained by contacting the accompanying consortia/group (e.g., MVP).