F251. Psychiatric Liability Genes are Linked to Oscillatory Brain Activity: A Genome-Wide Association Study

Abstract

Background: 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 the involvement of specific genetic variants, genes, and brain expression pathways remains elusive. Methods: We performed a genome-wide association study for the power of oscillations at frequencies (w2 Hz delta, w6 Hz theta, w10 Hz alpha, and w20 Hz beta) of the eyes-closed resting electroencephalogram (EEG) for 4.5M SNPs in N=8425 subjects. Next, we performed KGG positional gene-based analysis, and brain-expression analyses. Results: One significant SNP for alpha oscillation power is intronic to protein-coding gene PRKG2 (p<5x10-8). PRKG2 is deleted in the 4q21 microdeletion syndrome which results in speech and mental retardation. GABRA2da known genetic marker for alcohol use disorder and epilepsydsignificantly affected beta power, consistent with the known relation between GABAA interneuron activity and beta oscillations. Metaxcan (viz., SNP-based imputation of tissue expression levels using the GTEx expression database) revealed that hippocampal GABRA2 expression may mediate this effect. Twentyfour schizophrenia-linked genes at 3p21.1 were significant for alpha power (FDR q<0.05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex. Brain-expressed genes were significantly enriched. Conclusions: We successfully associated genes and genetic variants with oscillatory brain activity, some of which were previously associated with psychopathology (schizophrenia, alcohol use disorders). The results show that psychopathological liability genes affect brain functioning, and linked the genes' expression to specific cortical/subcortical brain regions.