In some circumstances, genetic correlations across disorders may arise from direct, potentially mutual, causation between the factor or disorder-specific liabilities and one another40 or reflect causation directly between the symptoms of different disorders41. Based on significant locus-specific violations of the four factor model at loci relevant to ALCH, we incorporated MR into Genomic SEM models, with both single and multi-variant MR indicating causal effects of ALCH on MDD and BIP.
