Subtype GWAS are not yet available from PGC MDD. As such, a major depressive disorder cohort was derived from the online mental health questionnaire in the UK Biobank (UKB MDD: 29,475 cases, 63,482 controls; Resource 22 on http://biobank.ctsu.ox.ac.uk) (18). The definition of major depressive disorder in this cohort is based on DSM-5, as described in full elsewhere (18), and in Supplementary Table 1 (7). We defined three major depressive disorder subtypes for analysis. Individuals meeting criteria for major depressive disorder were classed as recurrent cases if they reported multiple depressed periods across their lifetime (rMDD, N = 17,451), and single-episode cases otherwise (sMDD, N = 12,024, Supplementary Table 1). Individuals reporting depressive symptoms, but not meeting case criteria, were excluded from the main analysis but used as a “sub-threshold depression” subtype to examine the continuity of genetic associations with major depressive disorder below clinical thresholds (subMDD, N = 21,596). All subtypes were analysed with the full set of controls. Details on the quality control and analysis of the UK Biobank phenotypes is provided in the Supplementary Methods.
