In conducting this meta-analysis of major depression, we employed a pragmatic approach by including cohorts that met empirical criteria for sufficient genetic and phenotypic similarity. Our approach was cautious, clinically informed, guided by empirical data, and selective (e.g., we did not include cohorts with bipolar disorder (which requires MDD), depressive symptoms, neuroticism, or well-being). Approximately 44% of all major depression cases were assessed using traditional methods (PGC29, GenScot), treatment registers (iPSYCH, GERA; such approaches have been extensively used to elucidate the epidemiology of major depression), or a combination of methods (deCODE, UK Biobank) whereas ~56% of cases were from 23andMeD (via self-report)28. Multiple lines of genetic evidence supported conducting meta-analysis of these seven cohorts (e.g., out-of-sample prediction, sign tests, and genetic correlations).
