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Allelic Association of Human Dopamine D2 Receptor Gene in Alcoholism-Reply

Kenneth Blum, PhD; Ernest P. Noble, PhD, MD
JAMA. 1990;264(14):1808-1809. doi:10.1001/jama.1990.03450140027016.
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In Reply.—  Two types of genetic approaches are used in finding disease susceptibility genes: linkage analysis and association analysis.1 Because alcoholism is a heterogeneous disorder consisting of a variety of clinical subtypes, we chose for our initial investigation an association study by concentrating on candidate genes, as suggested by previous alcoholism research. Our primary candidate was the dopamine D2 receptor (DD2R) gene, since the dopaminergic system has been strongly implicated in drug-seeking (alcohol and cocaine) behavior. Brain samples were selected for two reasons. First, by concentrating on individuals with high proportions of severe alcoholism, we hoped for enriched alleles that may be associated with this form of the disease. Second, if a genetic association with alcoholism is found, then the availability of the same brain samples would permit studies of gene expression. In the case of the DD2R gene, its expression occurs in the brain, but has not


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