Several methodological aspects should be discussed. First, we evaluated depression continuum by combining cases from clinical populations diagnosed with MDD and participants from the general population who had been assessed for depressive symptoms. Such an inclusive approach may increase heterogeneity of the phenotype especially because lifetime MDD was evaluated whereas depressive symptoms indicate past weeks only. If anything, such approach would cause an underestimation of the effects as less information on depressive symptoms were obtained. However, the advantages of a large sample can outweigh the disadvantages of a less precisely defined phenotype. This has been observed in the GWAS of educational attainment which was successfully used as a proxy for intelligence (47). Our additional replication analysis showed that increasing the sample size yielded a stronger association of the top hit with depression continuum. It is complex to calculate statistical power of the current analysis as quantitative and qualitative measures were combined. In the current study, a genetic association with the depression continuum may reflect an effect on broad depressive phenotypes but could also be accounted for by an association with
