ISBD Keynote Abstracts

While bipolar disorder is highly heritable, the underlying disease mechanisms remain largely unknown.To gain greater insight, the Psychiatric Genomics Consortium Bipolar Disorder Working Group performed the largest genome-wide association study (GWAS) meta-analyses of bipolar disorder, combining Clinical, Community (biobank, registries) 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.Follow up functional analyses with finemapping and integration of eQTL data implicated 47 credible genes, which suggest involvement of synapse function and implicated neuronal tissue and regions in the etiology of bipolar disorder.The genetic architecture of bipolar disorder in Clinical and Community samples was largely overlapping, while Self-report samples had less overlap.The Self-report samples were more similar to bipolar disorder type II than to bipolar disorder type I, potentially reflecting a non-hospitalized, non-psychotic portion of the bipolar disorder spectrum.