Genetic diversity enhances gene discovery for bipolar disorder

Abstract

AbstractBipolar disorder (BD) is a severe, highly heritable mental illness. The underlying mechanisms remain largely unknown. To gain greater insight, we performed the largest genome-wide association study (GWAS) meta-analyses of BD, combining clinical and community (biobank and self-report) samples of European, East Asian, African American and Latino ancestry. We detected 337 independent genome-wide significant variants mapped to 298 loci in the multi-ancestry meta-analysis, a 4-fold increase over previous findings, and a novel ancestral-specific locus in the East Asian cohort. Fine-mapping and integration of eQTL data implicated 47 credible genes in the etiology of BD. The genetic architecture of BD in community-based samples was more similar to BD type II than to BD type I, potentially reflecting a non-hospitalized, non-psychotic portion of the BD spectrum.