Shared molecular genetic risk of alcohol dependence and posttraumatic stress disorder (PTSD).

Abstract

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur, highlighting the importance of understanding the etiology of these comorbid conditions. Although AUD and PTSD are moderately heritable with modest overlap in genetic risk as estimated from family studies, there has been a paucity of work using molecular genetic data to estimate shared genetic effects on these conditions. This study used large-scale genomewide molecular data to examine shared genetic risk for AUD, specifically alcohol dependence (AD), and PTSD through cross-trait linkage disequilibrium (LD) score regression (LDSC; also known as LDSR). Summary statistics came from the Psychiatric Genomics Consortium (PGC) PTSD Workgroup Freeze 2 European ancestry (EA) participants (N = 174,659) and AD summary statistics in EA participants (N = 38,686) came from the PGC Substance Use Disorders (SUD) Workgroup. We performed LDSC to estimate genetic correlation between AD and PTSD using HapMap3 variants and LD scores from the 1000 Genomes project. A moderate, significant correlation was observed between AD and PTSD (rg = .35, p = .02), with sex differences identified through stratified analyses. Our results are the first to demonstrate evidence of a shared molecular genetic etiology for AD and PTSD. Further research is needed to better understand possible sex differences in shared heritability and extend these results to additional populations.

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

“…Consistent with previous work (Sartor et al, 2011;Sheerin et al, 2020), this study found positive genetic correlations between PTSD and AUD-related phenotypes (Max. Alc., AUDIT-P, AUD, AD) among individuals of EA.…”

“…However, this effect was driven by women, for whom the genetic correlation was moderate and significant, but not for men (Sheerin et al, 2020). Genetic correlation analyses between PTSD and alcohol consumption were also conducted by our group, finding a non-significant association (rG = -.07; Bountress et al, 2021); another group found near zero genetic correlation between PTSD and the Alcohol Use Disorders Identification Test (AUDIT) consumption score subscale (AUDIT-C) (Mallard et al, 2021).…”

Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study

“…However, recent large GWAS metanalyses for AC and problematic alcohol use have yielded 99 (Liu et al, 2019) and 29 (Zhou et al, 2020) robustly associated variants, respectively. Few studies to date have examined the genetic correlation between PTSD and AUD using molecular genetic techniques such as linkage disequilibrium score regression (Bulik‐Sullivan et al, 2015), but recent research by our group found a moderate, significant correlation between PTSD and AD (rg = 0.35, Sheerin et al, 2020). To our knowledge, studies have yet to estimate genetic correlations between PTSD and AC.…”

Pathways to post‐traumatic stress disorder and alcohol dependence: Trauma, executive functioning, and family history of alcoholism in adolescents and young adults

“…alcoholism, executive function, post-traumatic stress disorder, trauma (r = .35) and a moderate, but significant correlation between alcohol dependence and PTSD (r = .34) in female participants (Sheerin et al, 2020). Although there are environmental and genetic contributions to both PTSD and alcohol dependence, most studies only examine dichotomous parental alcohol dependence status.…”

“…Further, Sartor et al showed that PTSD and alcohol dependence had a genetic correlation of 0.54 (Sartor et al., 2011). In addition, a recent study by Sheerin et al on shared molecular genetic basis for alcohol dependence and PTSD showed lower heritability for PTSD and alcohol dependence ( h 2 = 0.18 and 0.09, respectively) and a significant correlation between alcohol dependence and PTSD ( r = .35) and a moderate, but significant correlation between alcohol dependence and PTSD ( r = .34) in female participants (Sheerin et al., 2020). Although there are environmental and genetic contributions to both PTSD and alcohol dependence, most studies only examine dichotomous parental alcohol dependence status.…”