To investigate the polygenic nature of this trait, we generated a genetic risk score from 17 SNPs (Supplementary Table 6) with p-values < 5×10−8 in the joint-analysis (Discovery 23andMe, PGC, and replication 23andMe) and tested for association of the weighted MDD GRS with reporting of related phenotypes, medication use, and age-at-onset (Table 3) in the combined discovery and replication cohort, adjusting for depression case/control status. The GRS was significantly associated (FDR < 0.05) with each of these phenotypes. Importantly, the MDD GRS significantly associated with an earlier-age-of-onset in cases (effect= −1.49 years per unit of log odds, standard error= 0.37, p-val= 6.1×10−5).
