Two examples illustrate the point. The first concerns fMRI measures which are difficult to obtain in large numbers of people. Hariri and colleagues reported that a polymorphism in the serotonin transporter gene (5-HTT) was associated with the response of the amygdala to fearful stimuli (Hariri et al. 2002). In a comparison of two groups of 14 individuals, carriers of the s allele at the 5-HTT gene promoter were found to exhibit an increased amygdala fearful response compared with those homozygous for the l allele (Hariri et al. 2002): the means of the two groups were 0·28 (s.d.=0·22) and 0·03 (s.d.=0·19) with respect to % blood-oxygen-level-dependent (BOLD) signal change for fearful stimuli compared to neutral stimuli. In comparison with the data we have reviewed, this represents an enormous effect size (equivalent to ∼40% of phenotypic variance) that could be detected at a significance threshold of 0·05 with just 18 subjects. This finding could be due to chance statistical fluctuation. Indeed, a subsequent study of 92 individuals (including 19 from the first study) carried out by the same group again showed a
