Missing heritability (i.e., the disparity between genetic effects identified in family/twin studies and molecular genetic studies) in GWAS has been attributed to the emphasis on common genetic variants that have low penetrance (i.e., the proportion of individuals carrying a particular allele/genotype that also express a particular behavior). As the number of variants tested on GWAS platforms has evolved from testing thousands of variants to more than 1 million, the likelihood of capturing variants that are in LD with rare variants has increased. Current 1M chip platforms have identified hundreds of possible candidate variants for AD, but only a few of these have replicated across independent samples and have functional implications. Altogether, these observations suggest that when treated individually, common variants, such as SNPs, and rare variants, such as copy number variants, account for a small fraction of the missing heritability of diseases (Orozco et al., 2010). The most likely solution to this problem would be the incorporation of both common and rare genetic variants in genetic studies of alcohol using whole genome sequencing platforms. Unfortunately, a noteworthy drawback to the
