Numerous technologies have demonstrated that AD is a function of genetic differences, gene expression differences, protein-level differences, and differences in environmental exposure. Genetic association studies have uncovered genetic variants and environments that explain individual differences in susceptibility to AD. Genomewide association studies of alcohol indicate that its genetic etiology is highly complex. Transcriptome and proteome studies have shown differences in gene and protein expression in candidate tissues affected by alcohol and other drugs. Collectively, variability across these different systems may contribute a greater understanding of alcohol dependence; however, future strategies will require modeling techniques that capture ubiquitous principles that underlies all biological processes and complex diseases, epistasis and pleiotropy. Challenges for future genetic studies of alcohol, will be (1) the identification of phenotypes that assist in the assessment of how genetic variation in different neural systems influence and relate to different developmental stages of alcohol dependence, (2) the development and application of computational techniques that model the cumulative and combinatorial effects of genes and environments in a systematic manner, (3) the incorporation of a consistent set of proximal (e.g., peers)
