We identified five ways that MDD could be defined in the UK Biobank. First, self-reports of participants seeking medical attention for depression or related conditions provided ‘help-seeking’ definitions of MDD (referred to as ‘broad depression’ in a previous GWAS3). Second, participants were diagnosed with ‘symptom-based’ MDD if, in addition to meeting help-seeking criteria, they reported ever experiencing one or more of the two cardinal features of depression (low mood or anhedonia) for at least 2 weeks16. Third, a ‘self-report’ definition of MDD was based on participants’ self-reports of all past and current medical conditions to trained nurses. Fourth, an electronic medical record (EMR) definition was derived from the International Classification of Diseases, Tenth Revision (ICD-10) primary and secondary illness codes in electronic health records. Finally, a ‘CIDI-based’ diagnosis of lifetime MDD was available from individuals who answered an online ‘Mental Health Follow-up’ questionnaire (MHQ)17 based on the Composite International Diagnostic Interview Short Form (CIDI-SF)18, which included the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD (Supplementary Note, Supplementary Fig. 1 and Supplementary Table 2). None
