there has only been one replicated finding. Two studies have reported associations between ERN amplitude and a polymorphism of the DRD4 receptor gene (Agam et al., 2014; Kramer et al., 2007). However, whereas this SNP accounted for approximately 13% of the variance in ERN amplitude in the initial study of Kramer et al., it only accounted for about 3% of variance in the subsequent study of Agam and colleagues (the “winner's curse”; Ioannidis, 2008), and this latter effect was statistically significant only because a one-tailed test was used. In light of Figure 1, 3% is almost certainly a gross overestimate of the true effect. Moreover, subjects in Kramer et al. were selected from a larger group based on their genotypes (they were required to be homozygous for both the DRD4 receptor and COMT genes), creating a problem of interpretation, and the DRD4 gene was unrelated to BOLD activation of the dorsal anterior cingulate cortex (dACC) in Agam et al. In reinforcement learning accounts of the ERN, prediction error in the dACC is directly related to ERN amplitude (Holroyd & Coles, 2008). Failure to find an association between DRD4 and dACC activity throws the finding of association between DRD4 and ERN
