Ten traits associated with BD from clinical and epidemiological studies were investigated in detail for genetic and potentially causal relationships with BD via LDSC35, generalized summary statistics-based Mendelian randomization (GSMR)51, and bivariate gaussian mixture modeling49. BD has been strongly linked with sleep disturbances52, alcohol use53 and smoking54, higher educational attainment55,56, and mood instability57. Most of these traits had modest but significant genetic correlations with BD (rg = −0.05–0.35) (Fig. 3). Examining the effects of these traits on BD via GSMR, smoking initiation was associated with BD, corresponding to an OR of 1.49 (95% CI 1.38–1.61) for developing the disorder (P = 1.74 × 10−22) (Fig. 3). Testing the effect of BD on the traits, BD was significantly associated with reduced likelihood of being a morning person and increased number of drinks per week (P < 1.47 × 10−3) (Fig. 3). Positive bi-directional relationships were identified between BD and longer sleep duration, problematic alcohol use, educational attainment (EA), and mood instability (Fig. 3). Notably, the instrumental variables for mood instability were selected from a GWAS conducted in the general population, excluding
