Early investigations supporting P300 as a candidate endophenotype examined the healthy relatives of affected individuals. A seminal study by Begleiter and colleagues (Begleiter, Porjesz, Bihari, & Kissin, 1984) reported that P3AR was evident among 11-year-old male children of alcoholic fathers. Because boys in this study had not yet begun experimenting with alcohol, P3AR could not be due to effects of alcohol use per se, instead suggesting that it reflected genetic risk for alcoholism. Although replication failures have been reported, a meta-analysis of 30 studies of male youth with alcoholic parentage confirmed the initial findings (Polich, Pollock, & Bloom, 1994). Subsequent investigations further support P3AR as an endophenotype by showing that over the short term, P300 test-retest reliability is high (e.g., Hall et al., 2006; van Beijsterveldt, van Baal, Molenaar, Boomsma, & de Geus, 2001). It is also heritable. A recent meta-analysis of twin and family studies produced a pooled heritability estimate of approximately .60 (van Beijsterveldt & van Baal, 2002), and heritability appears to change little through middle adulthood (Smit, Posthuma, Boomsma, & de Geus, 2007). At least two studies
