QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 [71,73] are syntenic to a region on human chromosome 1q where several studies have identified QTLs for alcohol-related phenotypes [69,77,78]. The gene encoding 5-hydroxytryptamine receptor 1B (Htr1b) is located in this region, and mice in which this gene was knocked out were more aggressive and drank more alcohol, although the effects on alcohol consumption were influenced by unknown environmental factors in different laboratories [79]. In humans, HTR1B was subsequently associated with 'antisocial alcoholism (the dual diagnosis of alcoholism and antisocial personality disorder)' in two populations [80]. A QTL for severity of alcohol dependence and withdrawal on human chromosome 15 was identified in two human studies [77,81] and is syntenic with a region on mouse chromosome 9, where QTLs for alcohol preference have also been mapped [82,83]. Significant concordance between allelic variants of human GWASs and orthologous genes associated with alcohol-related phenotypes in mice [84,85] further demonstrate that mapping genes that underlie alcohol-related behaviors in mice is useful for identifying genes that govern alcohol-related phenotypes in people.
