First, the heritabilities of depression defined by minimal phenotyping strategies are lower than those of MDD defined by full DSM-5 criteria using the CIDI questionnaire. Second, although there is substantial genetic correlation between definitions, much of the shared genetic liability is not specific to MDD and significant differences remain, indicating the presence of genetic effects unique to each definition. Third, a larger percentage of the genome contributes to the shared genetic liability between minimal phenotyping definitions of depression and other psychiatric conditions than that between CIDI-based MDD and other conditions, likely driven by misdiagnosis due to nonspecific phenotyping. Fourth, all GWAS hits from the GPpsy minimal definition of depression are shared with genetically correlated conditions such as neuroticism and smoking. Finally, while minimal phenotyping definitions enable greater predictive power for MDD status in independent cohorts, this is due to the large sample size rather than indexing of MDD-specific effects. These results point to the nonspecific nature of genetic factors identified in minimal phenotyping definitions of depression.
