There is substantial information supporting the role of genetic factors in the susceptibility for alcohol dependence. However, the identification of specific genes that contribute to this predisposition has proven elusive, although several theoretically relevant candidates, e.g. DRD2 or 5-HT1B, have been considered. The difficulty in identifying specific genes may be related to the clinical heterogeneity of the disorder resulting in a poorly defined phenotype for genetic analysis. An alternative approach to the use of a diagnostic phenotype for identifying alcoholism susceptibility genes may lie in the examination of the neurobiological correlates of the disorder, the so-called endophenotypes. One possible endophenotype of alcohol dependence may be related to the P300 waveform of the event-related brain potential (ERP). Using data obtained from the Collaborative Study on the Genetics of Alcoholism (COGA), a multi-site family-based study, the utility of P300 amplitude as an endophentype was examined. Differences in P300 amplitude were found between alcoholics and nonalcoholics, between unaffected relatives of alcoholics and relatives of controls, as well as between unaffected offspring of alcoholic fathers and offspring of controls. A genetic analysis indicated that attributes of the P3 ERP waveform are heritable, and a quantitative trait locus analysis found linkage to several chromosomal regions. These data provide significant support for P300 as an endophenotype for alcohol dependence.

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