The strongest signal in the published GAIN-MDD GWAS was in PCLO (P = 7.7 × 10−7)5, encoding Piccolo, a protein involved in cycling of synaptic vesicles including at monoaminergic synapses. The association was supported in only one of five follow-up datasets (that totaled 6,079 cases and 5,893 controls), and it (like GAIN-MDD) was population-based, suggesting possible phenotypic heterogeneity. P-values in PCLO were less significant in our meta-analyses (~10−5) than in GAIN-MDD alone. Recurrent early-onset cases provided most of the evidence for association in GAIN-MDD, but the lowest P-value in the GenRED sample was 0.017. We have no independent data to test whether association is stronger in population-based samples.
