Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders

Abstract

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B = 0.126, p < 0.001), alcohol dependence (B = 0.231, p < 0.001), and cocaine dependence (B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.

Fig. 1. Main and interaction effects of PGC-PTSD PRS and sex on DSM-IV PTSD and substance dependence in COGA.

Note: Parameter estimates (and standard errors) are displayed only for statistically significant pathways that remained significant after adjusting p-values for multiple testing using the Benjamini–Hochberg procedure. Not pictured, but also included in this model as covariates, are age, principal components, genotype array, and cross-term covariate interactions.

Fig. 2. Associations between PGC-PTSD PRS*Alcohol dependence and DSM-IV PTSD and substance dependence in COGA.

Note: Parameter estimates (and standard errors) are displayed only for statistically significant pathways that remained significant after adjusting p-values for multiple testing using the Benjamini–Hochberg procedure. Not pictured, but also included in this model as covariates, are sex, age, principal components, genotype array, and cross-term covariate interactions.