Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.

Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta 4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene-based analysis and brain-expression analyses. GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABAA interneuron activity and beta oscillations. Tissue-specific SNP-based imputation of gene-expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty-four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions.

Personality and Substance Use Disorders: I. Effects of Gender and Alcoholism Subtype.

The relationship between alcoholism and self-rated personality was explored in a community-ascertained sample of 303 male and 103 female alcoholics, and 304 male and 770 female nonalcoholics. Alcoholics met DSM-Ill-R lifetime criteria for alcohol dependence; personality was assessed using the Multidimensional Personality Questionnaire. Compared with controls, alcoholics scored significantly higher on all indicators of negative emotionality, and consistently lower on all indicators of constraint. Individual effect sizes were moderate in both the male and female samples. A subsample of severe male alcoholics, identified by cluster analysis, was characterized by relatively early onset of problem drinking and relatively high antisociality and familial loading of problem drinking; they were also more extreme than moderate male alcoholics on negative emotionality and constraint. When taken in aggregate, personality risk appears to be associated with a continuum of alcoholic risk such that individuals extreme in both negative emotionality and behavioral disinhibition have especially high rates of alcoholism.

Identifying shared environmental contributions to early substance use: the respective roles of peers and parents.

Although behavior genetic studies have suggested that early substance use is primarily environmentally mediated, no study has sought to identify the specific sources of environmental variance. Using data obtained from multiple informants, this study assessed the contributions of peer deviance and parent-child relationship problems to substance use in 14-year-old male and female twins (N = 1,403) drawn from the Minnesota Twin Family Study (MTFS). All three phenotypes were influenced primarily by shared environmental variance (average c(2) =.51), as was the overlap among them. Moreover, peer deviance and parent-child relationship problems accounted for approximately 77% of the variance in early substance use. Findings also indicated that peer deviance, but not parent-child relationship problems, accounted uniquely for variance in early substance use.