Differential shared genetic influences on anxiety with problematic alcohol use compared to alcohol consumption

Abstract Anxiety disorders and alcohol use disorders are common psychiatric illnesses. Comorbidity of the two disorders can have a tremendous effect on treatment of one or both disorders, as well as an individual’s social, economic, and physical well-being. We estimated genome-wide genetic correlations between anxiety and alcohol use traits using linkage disequilibrium score regression (LDSC) and found strong and positive correlations of anxiety with problematic alcohol use (PAU), but not with most alcohol consumption (AC) measures. We observed strong, positive between-sex genetic correlations for all traits, but found suggestive evidence that the genetic correlation between alcohol use and anxiety might differ between males and females. Estimates of local genetic covariance demonstrated divergent genetic covariance profiles of PAU and AC with anxiety phenotypes and localized 12 specific genomic regions that likely contribute to both anxiety and alcohol use. Finally, partitioning the genetic covariance among functional annotations also identified the amygdala, caudate basal ganglia and frontal cortex as contributing significantly to positive genetic covariance between anxiety and PAU phenotypes. This study serves as a framework for an approach to be used in future analyses of the genetics of comorbid disorders.