To date, mouse alcohol response QTL analyses have not detected consilience with the site on human chromosome 4 near the ADH gene cluster, which has been replicated repeatedly in human studies. While it is not known for certain what genes are responsible for the QTL on chromosome 4 there is some evidence from human studies that ADH1B may contribute to the association (Ehlers et al., 2004; MacGregor et al., 2008). Numerous candidate gene studies have also provided evidence for association with ADH gene polymorphisms and alcohol dependence in human studies (see Edenberg et al., 2006). If ADH polymorphisms do account for most of the QTL on human chromosome 4 then the present data may suggest that variations in ADH are less functionally linked to alcohol-related phenotypes in mice than in humans. This may also reflect that fact that one advantage of animal studies is that ethanol metabolism and resulting differences in blood/brain alcohol concentrations can be and frequently are controlled for statistically, which would serve to mitigate detection of ADH or other ethanol metabolism genes as QTLs in many animal
