Differences in genetic correlations between posttraumatic stress disorder and alcohol-related problems phenotypes compared to alcohol consumption-related phenotypes

Abstract

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-alcohol-related problems 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 and a range of alcohol consumption-related and alcohol-related problems phenotypes.

Results: In EAs, there were positive genetic correlations between PTSD phenotypes and alcohol-related problems phenotypes (e.g. Alcohol Use Disorders Identification Test (AUDIT) problem score) (rGs: 0.132-0.533, all FDR adjusted p < 0.05). However, the genetic correlations between PTSD phenotypes and alcohol consumption -related phenotypes (e.g. drinks per week) were negatively associated or non-significant (rGs: -0.417 to -0.042, FDR adjusted p: <0.05-NS). For AAs, the direction of correlations was sometimes consistent and sometimes inconsistent with that in EAs, and the ranges were larger (rGs for alcohol-related problems: -0.275 to 0.266, FDR adjusted p: NS, alcohol consumption-related: 0.145-0.699, 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 high levels of alcohol consumption are not the same as those that lead someone to develop PTSD and alcohol-related problems. Discussion around needing improved methods to better estimate heritabilities and genetic correlations in diverse and admixed ancestry samples is provided.

Keywords: Alcohol consumption; alcohol use disorder; genetic correlation; posttraumatic stress disorder.

Fig. 1.

Genetic Correlations of PTSD and Alcohol Phenotypes (±s.e. bars) – EA Note: Unadjusted significant p values ( p < 0.05) for r_Gs are noted with an asterisk. Those passing FDR adjustment are noted with an additional asterisks (total of two asterisks for those passing FDR adjustment). PTSD, Posttraumatic Stress Disorder; EA, European ancestry; s.e., standard error; DPW, Drinks per Week; GSCAN, GWAS & Sequencing Consortium of Alcohol and Nicotine Use; UKB, UK Biobank; AUDIT, Alcohol Use Disorder Identification Test; T, total; P, problems; C, consumption; Max. Alc., Maximum Alcohol Intake; AUD, Alcohol Use Disorder; AD, Alcohol Dependence; PGC, Psychiatric Genomics Consortium; Re-exp., reexperiencing; MVP, Million Veteran Program. Alcohol phenotypes are ordered from more typical to more problematic (top to bottom) and color coded by each type of phenotype (i.e., DPW, AUDIT-C, AUDIT-T, Max. Alc., AUDIT-P, AUD, AD) to draw attention to difference in findings.

Fig. 2.

Genetic Correlations of PTSD and Alcohol Phenotypes (± s.e. bars) – AA. Note: Unadjusted significant p values ( p < 0.05) for r_Gs are noted with an asterisk. Those passing FDR adjustment are noted with an additional asterisks (total of two asterisks for those passing FDR adjustment). PTSD, Posttraumatic Stress Disorder; AA, African ancestry; s.e., standard error; AUDIT, Alcohol Use Disorder Identification Test; C, consumption; Max. Alc., Maximum Alcohol Intake; AUD, Alcohol Use Disorder; AD, Alcohol Dependence; PGC, Psychiatric Genomics Consortium; Re-exp., reexperiencing; MVP, Million Veteran Program. Alcohol phenotypes are ordered from more typical to more problematic (top to bottom) and color coded by each type of phenotype (i.e., AUDIT-C, Max. Alc., AUD, AD) to draw attention to difference in findings.