estimated to be 18.6% (s.e. = 0.008, P = 5.1 × 10−132) on the liability scale, assuming a BD population prevalence of 2%, and 15.6% (s.e. = 0.006, P = 5.0 × 10−132) assuming a population prevalence of 1% (Supplementary Table 3). The genomic inflation factor (λGC) was 1.38 and the LD Score regression (LDSC) intercept was 1.04 (s.e. = 0.01, P = 2.5 × 10−4) (Supplementary Fig. 1). While the intercept has frequently been used as an indicator of confounding from population stratification, it can rise above 1 with increased sample size and heritability. The attenuation ratio—(LDSC intercept - 1)/(mean of association chi-square statistics - 1)—which is not subject to these limitations, was 0.06 (s.e. = 0.02), indicating that the majority of inflation of the GWAS test statistics was due to polygenicity35,36. Of the 64 genome-wide significant loci, 33 are novel discoveries (i.e. loci not overlapping with any locus previously reported as genome-wide significant for BD). Novel loci include the major histocompatibility complex (MHC) and loci previously reaching genome-wide significance for other psychiatric disorders, including 10 for schizophrenia, 4 for major depression, and 3 for childhood-onset psychiatric disorders or problematic alcohol use (Table 1).
