One particular challenge of the post-genomic “big data” era is to determine the degree to which alterations in gene expression networks and gene structure can be used as predictive models that infer causal relationships associated with AUD. For example, there is accumulating genomic evidence for alcohol-induced inflammatory-and immune-related signaling from genetic association studies in alcoholics (Edenberg et al., 2008; Pastor et al., 2000; Pastor et al., 2005; Saiz et al., 2009), gene expression microarray studies in postmortem brains of alcoholics (Liu et al., 2006; Ökvist et al., 2007), and transcriptome meta-analyses in selectively bred (Mulligan et al., 2006) and ethanol-exposed mice (Gorini et al., 2013a; Gorini et al., 2013b; Nunez et al., 2013; Osterndorff-Kahanek et al., 2013). Network analyses have identified highly connected hub genes that are related to inflammatory/immune responses and mediate their effects through NF-κB. These studies implicated inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) as having a modulatory role in alcohol drinking. In a proof-of-concept study, Truitt and colleagues showed that pharmacological and genetic inhibition of IKKβ decreased voluntary ethanol consumption, providing initial support for
