We used MR to investigate the relationship between major depression and schizophrenia. Although major depression had positive rg with many psychiatric disorders, only schizophrenia has sufficient associations for MR analyses. We found significant bi-directional correlations in SNP effect sizes for schizophrenia loci in major depression (PGSMR=1.1×10−40) and for major depression loci in schizophrenia (PGSMR=1.5×10−11). These results suggest that the major depression-schizophrenia rg of 0.34 is consistent with partially shared biological pathways being causal for both disorders. Although it is plausible that diagnostic misclassification/ambiguity (e.g., misdiagnosis of MDD as schizoaffective disorder) could contaminate these analyses, levels of misclassification would need to be implausibly high (30% unidirectional, 15% bidirectional) to result in an rg of ~0.3REF65.
