In summary, it can be reasonably concluded from the preceding discussion of candidate genes identified for alcohol dependence represent bona fide variants that function to alter the phenotype. The majority of these genes were identified in “high-risk” or homogenous populations which resulted in relatively dramatic effects on the phenotype, such as the stop codon found HTR2B which was associated with a very severe early on-set form of alcoholism in individuals that are also characterized as violent criminal offenders and display extreme impulsivity (Bevilacqua and Goldman, 2013). This example highlights the beneficial use of intermediate phenotypes (such as impulsivity) to help guide gene identification, especially in homogenous populations such as in the Finnish population in which this study was conducted. However, the candidate gene approach in particular is useful only to a certain threshold when gene effect sizes are considered. To fully understand the complexity of the genetics of AUD, genes with a range of effect sizes need to be identified because it is almost a certainty that both gene variants with large effects and many variants of small effect will ultimately explain the substantial phenotypic variability in AUD.
