Evidence for genetic correlation of DSM-IV opioid dependence and childhood trauma based on additive genome-wide effects

Purpose: The unprecedented increases in morbidity and mortality associated with the opioid epidemic are indicative of the worst drug epidemic in US history. Previous research has demonstrated a moderate genetic correlation... [ view full abstract ]

Purpose: The unprecedented increases in morbidity and mortality associated with the opioid epidemic are indicative of the worst drug epidemic in US history. Previous research has demonstrated a moderate genetic correlation (r_G=.49) between interpersonal trauma and generalized vulnerability to drug dependence (Palmer et al., 2016). The current study aims to expand on this work and investigate whether common genetic markers implicated in childhood trauma are implicated in opioid dependence (OD).

Methods: Genome-wide data (N=3,894 unrelated individuals) were drawn from several studies and imputed, including the Comorbidity and Trauma Study, Heroin Dependence in Western Australia, OZ-ALC, and ongoing genetic studies of substance dependence at Yale. Case/control genomic-relatedness-matrix restricted maximum likelihood estimation was used to determine the proportion of variance in each phenotype attributed to additive genetic variance (h²_SNP). Bivariate models were used to determine the genetic correlation (r_G-SNP) across the phenotypes. Analyses controlled for sex, age, and other drug dependence and parameter estimates for OD were adjusted using a transformation to a liability scale based on disease prevalence in the population. A subset of individuals (N=1,346) had data on childhood trauma.

Results: Moderate additive genetic influences on OD, h²_SNP-OD=.41 (SE=.03, p<.001) are partially shared with additive genetic effects on childhood trauma, h²_SNP-Trauma=.44 (SE=.24, p=.03); r_{G-SNP-OD-Trauma}=.48 (SE=.06, p<.001). The heritability of OD for males and females was similar (h²_SNP-Males=.47, SE=.06, p<.001; h²_SNP-Females=.33, SE=.08, p<.001) and highly correlated, r_{G-SNP-Males-Females}=.87 (SE=.16, ###i

/i###<.001).

Conclusion: Findings suggest that a moderate portion of the additive genetic effects on trauma is shared with the additive genetic effects on OD. Further, the high r_G-SNP across males and females for OD indicates that largely the same polymorphisms contribute to heritability across each sex, despite findings from previous literature suggesting that genetic influences across males and females may be differential. Potential reasons for this overlap will be discussed along with trends of h2SNP stratification across the genome.