Although many genes are differentially expressed in the brains of alcoholic subjects, the observed fold-changes in individual genes are relatively small. Overall expression differences between alcohol-dependent cases and matched healthy controls often range from 20–50% (Liu et al., 2006). This is consistent with genome-wide association studies (GWAS) showing that multiple genes influence the risk for AUD, while individual genes contribute a relatively small effect (e.g., SNP odds ratios are typically <1.5 with individual SNP heritability of ~1–2%) (Agrawal and Bierut, 2012; Edenberg and Foroud, 2006; Gelernter et al., 2014). With the exception of some genes involved in alcohol metabolism (Zhang et al., 2014a) that we discuss later in this review, individual genes are not considered to be strong predictors of AUD susceptibility nor do they contribute to the majority of AUD pathophysiology. It is hypothesized 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 phenotypes (Farris et al., 2015b; Farris and Mayfield, 2014).
