However the penalty in sample size attributable to the imposition of a genome-wide significance may be much less than the penalty required to detect an even slightly smaller effect locus, which may be the case with the locus that the intermediate phenotype analysis has proposed for testing. The effect size found in the intermediate phenotype analysis is no guide to the effect size that the same locus exerts on the psychiatric disease. Assuming a slight reduction in the OR from 1.1 to 1.08, the required sample size jumps to 24,000 (i.e., 12,000 cases, 12,000 controls) [46], almost large enough to detect genome-wide significant signals for the loci with OR of 1.1 and above. In other words, the saving in sample size is not necessarily as large as first appears to be the case.
