For meta-analysis, we defined two phenotypic models: Broad (all 3,957 MDD cases from the three samples, vs. 3,428 controls), and Narrow (2,191 cases with onset before age 31 and recurrence, including GenRED chronic cases). We did not require positive family history because STAR*D and GAIN-MDD assessed this by proband response to a single question. Exploratory separate analyses of males and females were carried out for each phenotype, because women are at a two-fold increased risk, and twin studies suggest partial independence of genetic risk factors for women and men.22, 23 Characteristics of the three samples are summarized in Table 2.
