The overlapping hypotheses listed above imply that an association study for MDD has less power than for studies of many other complex genetic disorders. However, even if the hypotheses listed above were not the contributing factors, we may still conclude that insufficient power underpins the dearth of results from this mega-analysis by considering the epidemiology of MDD. MDD is highly prevalent in the population, implying that cases are less extreme in the population compared with the controls and therefore larger sample sizes are required. For example, we have calculated that sample sizes 2.4 times larger are needed for GWAS of MDD (prevalence 0.15) compared with schizophrenia (prevalence 0.007).25,87 Furthermore, if we assume as a first approximation that the number and frequency distribution of risk alleles is the same for MDD and schizophrenia, then samples sizes five times larger are needed to account for the lower heritability of MDD (0.37)10 compared with schizophrenia (0.81),88 implying lower effect sizes at each locus (see Wray et al.25 and Yang et al.87 for details). Obtaining a total sample size on the order of 100
