One justification for finding loci that influence an intermediate phenotype is that subsequently testing the involvement of the locus in psychiatric disease will require a smaller sample size than a genome-wide analysis, since investigators will not have to impose a significance threshold that takes into account multiple testing across the entire genome. At first sight, the saving appears impressive. Ignoring correlation between markers, the required corrected 0.05 significance threshold for testing 1 million markers expressed as a Z score, is 5.40 standard deviations. Testing a single variant requires a Z score of 1.96. The reduction in sample size is then approximately the square of 1.96/5.40, or 7.6 times smaller.
