The genetic correlation of BD with other psychiatric disorders was consistent with previous reports65,66. Our results also corroborate previous genetic and clinical evidence of associations between BD and sleep disturbances67, problematic alcohol use68, and smoking69. While the genome-wide genetic correlations with these traits were modest (rg = −0.05–0.35), MiXeR estimated that, for all traits, more than 55% of trait-influencing variants also influence BD (Fig. 3). Taken together, these results point to shared biology as one possible explanation for the high prevalence of substance use in BD. However, excluding genetic variants associated with both traits, MR analyses suggested that smoking is also a putatively “causal” risk factor for BD, while BD has no effect on smoking, consistent with a previous report70. (We use the word “causal” with caution here as we consider MR an exploratory analysis to identify potentially modifiable risk factors that warrant more detailed investigations to understand their complex relationship with BD.) In contrast, MR indicated that BD had bi-directional “causal” relationships with problematic alcohol use, longer sleep duration, and mood instability. Insights into the relationship of such behavioral
