Second, in some cases the behavioral QTGs identified will be the same in mouse and man (Mogil et al., 2003), and in other cases QTL research will identify networks of genes relevant to ethanol response in both mouse and man. For example, there is considerable evidence in the animal literature for a relationship between the Gabra1-Garba6-Gabrg2-Gabrb2 cluster of GABAA receptor genes and alcohol-related phenotypes, but evidence for their involvement in human alcohol dependence has been mixed (Dick et al., 2005, 2006b). However, other GABA-A receptor genes, such as GABRA2, have been robustly associated with alcohol dependence in human studies across multiple independent projects. (Covault et al., 2004, 2008; Edenberg et al., 2004; Lappalainen et al., 2005; Dick et al., 2006c; Fehr et al., 2006; Matthews et al., 2007). In another example, alcohol consumption is associated with the alpha-synuclein gene, SNCA, in alcohol preferring and alcohol non-preferring rats (Liang et al., 2003) and craving for alcohol in humans (Foroud et al., 2007), despite there being no association with clinical diagnoses in the sample. This underscores the importance of phenotype choice in gene identification efforts and the need to examine alcohol-related phenomena in addition to DSM alcohol dependence diagnoses.
