We conducted a set of pre-planned secondary analyses using the discovery samples. These analyses presume that observable clinical features allow the ability to index etiological genetic heterogeneity. The clinical features we chose—sex, age of onset, recurrence and typicality—had a rationale from genetic epidemiological studies, and were comparably assessed in most of the discovery samples (Supplementary Methods). The results are summarized in Table 2, and detail on regions with P<1×10−5 provided in Supplementary Table S21. Parallel analyses of chrX SNPs for these secondary phenotypes also failed to identify convincing associations. Given the level of resolution afforded by our sample size and genotyping, none of these clinical features successfully indexed the clinical heterogeneity of MDD (all λ1000 values were small and no P-value approached genome-wide significance). However, we note that the total samples available for these analyses were small for a GWAS of a complex and modestly heritable trait. Moreover, as described above, SNPs identified in analyses by sex and for recurrent MDD did not yield genome-wide significance in replication in external samples.
