The LCV model was used to infer genetic causal relationships between trait pairs using the 1000 Genomes Project European linkage disequilibrium reference panel. MDD-META was subjected to LCV with all traits described above for genetic correlation analysis. Due to differences in heritability calculation method and the number of SNPs used by LCV versus LDSC, genetic correlation results were not used to inform LCV trait pair selection. Genetic causality proportions (gĉp) were interpreted only when the heritability z-score of both traits was ≥ 7, as determined by LCV, not LDSC.43 Fully causal relationships were deduced for significant trait pairs with gĉp estimates ≥ 0.70; otherwise gĉp estimates were considered evidence for partial causality.43
