We computed genetic risk scores based on the 17 SNPs with p-values < 5e–8 in the joint analysis of 23andMe discovery, PGC, and 23andMe replication results, as a linear combination of independent single-SNP effect sizes estimated from that joint-analysis (Supplementary Table 2). We tested each secondary phenotype for association with these scores in the combined 23andMe discovery and replication cohorts; we tested for effects on age-of-onset in depression cases only (Table 3). For age-of-onset, we defined “early onset” as onset before age 30, and fit this binary outcome by logistic regression; we also fit a model for continuous age-of-onset using linear regression. In all these tests, we included covariates for age, gender, five PCs, and depression case/control status. In this way, we were testing for residual association not explained by depression status, and thus these associations are independent of the data that was used to identify these 17 variants. Separately, we tested each of the 17 SNPs individually for association with this same set of phenotypes, including the same covariates (Supplementary Table 7).
