In the discovery phase, we conducted mega-analysis for MDD using nine primary samples. All groups uploaded individual genotype and phenotype data to a central computer cluster, and the PGC Statistical Analysis Group conducted uniform quality control, imputation and association analyses. Mega-analysis and meta-analysis yield essentially identical results in theory38 and in practice.37 However, mega-analysis of individual phenotype and genotype data was used to allow more consistent quality control and analysis, disentangle the issue of control subjects used by multiple studies, allow conditional analyses and to enable efficient secondary analyses. In the replication phase, we evaluated the top loci in seven independent MDD samples and in the PGC BIP megaanalysis36 given the phenotypic and genetic overlap between MDD and BIP.39,40 Finally, we conducted exploratory analyses of MDD sub-phenotypes in an attempt to index clinical heterogeneity. Most of the primary genotype data and the results have been deposited in the NIMH Human Genetics Initiative Repository (Supplementary Methods).
