In a first genome-wide case-control association study (GWAS) of an ERO endophenotype (frontal theta ERO from the target response in visual oddball task), Zlojutro et al. [216] reported some important genetic associations. This was a two-stage GWAS study that first identified four markers, ARID5A, GNAS1, ANXA13, and HTR7 with nominally significant association with frontal theta ERO, with the most significance in ARID protein 5A gene (ARID5A) on chromosome 2q11. The most intriguing association was with a serotonin receptor gene (HTR7) on chromosome 10q23, implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. They also found a significant association of alcohol dependence diagnosis (DSM-IV) with several HTR7 SNPs among GWAS case-controls. Significant recessive genetic effects were also detected for alcohol dependence in both the COGA case-control and family-based samples, with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggested a role of the serotonergic system in the biological basis of alcohol dependence, and therefore demonstrated the utility of brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders such as alcoholism.
