Electrophysiological endophenotypes and polygenic risk scores for substance misuse

Recent work from the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) has identified over 500 genetic variants associated with several substance misuse phenotypes. We previously evaluated the genetic basis of 17... [ view full abstract ]

Recent work from the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) has identified over 500 genetic variants associated with several substance misuse phenotypes. We previously evaluated the genetic basis of 17 endophenotypes, including antisaccade, P300 amplitude, and resting EEG power, that have been identified as relevant to problematic substance use behaviors and externalizing spectrum psychopathology. GWAS of these endophenotypes was performed using a community-based sample of over 4900 individuals, comprising adolescent twins and their biological parents, and the results were published as a special issue in Psychophysiology (Iacono, 2014). In a recent report, our group tested whether genetic variants relevant to schizophrenia were associated with individual differences in these psychophysiological endophenotypes (Liu et al., 2017). This exploratory study did not find a significant association between polygenic risk scores for schizophrenia and any of the 17 endophenotypes. However, because there is strong theoretical and empirical evidence that these endophenotypes are relevant to biological and cognitive systems implicated in externalizing and addictive behaviors, we hypothesized that these endophenotypes would relate to genetic variants associated with substance misuse/externalizing behaviors. The current project will focus on testing the association between these externalizing-related endophenotypes (P300 amplitude, resting EEG power, antisaccade performance) and a polygenic risk score for alcohol use (number of drinks per week; derived from the GSCAN study findings) in a community-based sample of over 4900 individuals genotyped on the Illumina 600W-Quad array. Results will have implications for the utility of psychophysiological endophenotypes to characterize the genetically-mediated neurophysiological systems implicated in externalizing and problematic substance use behaviors.