P-300 event-related potential amplitude as an endophenotype of alcoholism - Evidence from the collaborative study on the genetics of alcoholism

There is substantial information supporting the role of genetic factors in the susceptibility for alcohol dependence. However, the identification of s pecific genes that contribute to this predisposition has proven elusive, al though several theoretically relevant candidates, e.g. DRD2 or 5-HT1B have been considered, The difficulty in identifying specific genes may be relate d to the clinical heterogeneity of the disorder resulting in a poorly defin ed phenotype for genetic analysis. An alternative approach to the use of a diagnostic phenotype for identifying alcoholism susceptibility genes may li e 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 P-300 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 P-300 am plitude as an endophentype was examined, Differences in P-300 amplitude wer e found between alcoholics and nonalcoholics, between unaffected relatives of alcoholics and relatives of controls, as well as between unaffected offs pring of alcoholic fathers and offspring of controls. A genetic analysis in dicated that attributes of the Pg ERP waveform are heritable, and a quantit ative trait locus analysis found linkage to several chromosomal regions. Th ese data provide significant support for P-300 as an endophenotype for alco hol dependence. Copyright (C) 2001 National Science Council, ROC and S. Kar ger AG. Basel.