We next examined the specificity of the action of individual genetic loci found in GWAS of each definition of MDD. We found that the help-seeking definitions gave the greatest number of genome-wide-significant loci (27 from GPpsy and Psypsy; Supplementary Table 10) in GWAS, consistent with their larger sample sizes and statistical power for finding associations. We examined whether these loci could be detected in strictly defined MDD. Of the 27 loci from minimal phenotyping definitions, 10 showed significant effects (at P < 0.05 after multiple-testing correction for 27 loci) on LifetimeMDD, despite the latter’s much smaller sample size, consistent with the hypothesis that risk loci for minimal phenotyping MDD also act in strictly defined MDD. However, all ten loci also showed significant effects in neuroticism, smoking, schizophrenia and the no-MDD help-seeking condition (GPNoDep; Supplementary Table 19). Furthermore, all significant SNPs in minimal phenotyping definitions of depression had the same directions of effect on no-MDD phenotypes (Fig. 6).
