In conclusion, this two-stage GWAS has identified four genes that may contribute to the expression of event-related theta oscillations measured in the frontal region of the brain and are worthy of further investigation: ARID5A, GNAS1, ANXA13, and HTR7. Of these four, the serotonin receptor gene HTR7 also appears to play a role in the risk for alcohol dependence, with a significant association emerging in the case-control samples for intronic marker rs7916403. The risk allele for rs7916403 has an OR of 1.24 for an additive measured genotype model, although significant recessive effects for diagnoses of alcohol dependence were detected for both sample sets that notably parallel the theta ERO deficits observed among corresponding T/T homozygotes. Haplotype-based tests of HTR7 LD blocks lend support to these findings, revealing significant omnibus association with alcohol dependence, with important effects contributed by the rs7916403 variant. Therefore, the results of the study are compelling, implicating the serotonergic system in the genetic susceptibility of alcohol dependence, although further research is needed to fully determine the functional importance of 5-HT7 in the generation of theta EROs and its contribution to the biological basis of alcohol dependence.
