While the available GWAS data do not indicate that intermediate phenotypes will necessarily be any more genetically tractable than psychiatric disease, there is one important proviso: even a small increase in the mean locus-specific effect size has a substantial impact on power (given that power is proportional to the square of the effect size). Consistent with the notion that height and weight are more complex phenotypes (that is, less biologically coherent) than lipid levels, locus-specific effects are smaller: the mean effect size for 180 loci on height is 0.058% of phenotypic variance [41] and mean effect on weight is 0.045% of phenotypic variance for 32 loci [42]. These figures are lower than the effects found for lipids and red cell phenotypes. Thus while more than 50,000 subjects may be needed to detect a single locus contributing to major depression susceptibility [43], a comparable figure for an intermediate phenotype might be less than 10,000. Consequently, genetic analysis of the latter may be a preferable first step (cheaper and quicker) than studying disease.
