Although we identified several genes that were differentially expressed in the PFC of alcohol-dependent subjects, the variance explained by individual genes was very small (0.15–1%). The differential expression observed here is smaller than that reported in earlier differential expression studies of alcoholism, but it is consistent with differential expression studies of larger sample size37. For example, the CommonMind consortium reported similar fold changes in the differential expression study of schizophrenia and they showed that their observation is consistent with plausible models for average differential gene expression and the polygenic inheritance of schizophrenia. The polygenicity of AD has also been observed by the GWAS of alcoholism and other complex behavioral/psychiatric disorders22,38–41, and it was demonstrated that effect size for each individual genetic variant is very small. Studies that used a co-expression network approach also showed that alcohol dependence is shaped, in part, by persistent alterations in networks of co-expressed genes that collectively mediate excessive drinking and other alcohol-dependent phenotypes8,9. These and other studies also demonstrated that the gene network structure is significantly correlated with lifetime alcohol consumption in addition to an
