Although the variance explained by these SNPs is small, we find that our cohorts identified by self-report of major depression are highly genetically correlated with cohorts identified by clinical interview, a result further corroborated by significant sign-test and effect size matching between the top 23andMe SNPs (nominal pval < 1×10−5) and their counterparts in PGC in self-report and clinical-interview datasets. To better understand the phenotypic characteristics of the 23andMe self-report subjects, we assessed reporting of medication use and comorbidities and found that all tested characteristics were significantly increased in the subjects reporting Depression, similar to what is seen in clinically ascertained subjects. Notably, many of the most significant SNPs show evidence of pleiotropy when examined in other clinically ascertained psychiatric disorders with the smallest p-values among individual SNPs seen for MDD SNPs in the PGC Schizophrenia and neuroticism datasets. This finding is unsurprising given the pleiotropy reported by other GWAS and cross-psychiatric analyses13, and lends further support to the relevance of a self-report phenotype to clinical disease.
