Why different rules are required for polygenic inheritance: lessons from studies of the DRD2 gene

In 1990 Blum, Noble and coworkers reported a significant association between the 1 allele of the Tarq1A polymorphism of the D2 dopamine receptor gene (DRD2) and severe alcoholism. Subsequently, some reports using both linkage and association techniques supported this finding whereas others either did not, or seemed not to support this association. Although some of the controversy is due to true variability in the frequency of the D2A1 allele in different groups of alcoholics and controls, some is also due to the frequent attempt to apply the rules of single-gene disorders to what is in all likelihood a multifactorial, polygenic disorder. When the rules that are appropriate to polygenic inheritance are used a significant portion of the controversy is resolved. Those rules, and their application to the role of the DRD2 gene in addictive, impulsive behaviors, are reviewed.