N Nature Neuroscience · Nov 25, 2025 Trans-ancestry genome-wide analyses of bipolar disorder in East Asian and European populations improve genetic discovery Genome-wide association studies (GWASs) of bipolar disorder (BD) have predominantly included individuals of European (EUR) ancestry, underrepresenting non-EUR populations and limiting insight into disease mechanisms. Here we performed a GWAS of BD in Han Chinese individuals (5,164 cases and 13,460 controls) and conducted comparative and integrative analyses with independent East Asian (EAS, 4,479 cases and 75,725 controls) and EUR (59,287 cases and 781,022 controls) cohorts from the PGC4 GWAS. Our GWAS in EAS ancestry identified two genome-wide significant risk loci, including variants at the major histocompatibility complex (MHC) class II region. Incorporating EAS data into trans-ancestry GWAS revealed 93 significant loci (23 novel). Heritability enrichment analyses implicated a variety of neuronal cell types. Multidimensional post-GWAS prioritization identified 39 high-confidence risk genes, of which 15 were differentially expressed in the brains of patients with BD, 12 modulated BD-relevant behaviors in mice and 18 are pharmacologically tractable. This work advances understanding of the biological underpinnings of BD and provides direction for future research in underrepresented populations. Bipolar disorder Genome-wide association studies biology mouse experiments
N Nature Neuroscience · Nov 11, 2025 A genome-wide analysis of the shared genetic risk architecture of complex neurological and psychiatric disorders Although neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathophysiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here we performed a comprehensive analysis of genome-wide association study data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic signal and biological associations. Using complementary statistical tools, we demonstrate that a large set of common genetic variants impacts the risk of multiple neurological and psychiatric disorders, even in the absence of genetic correlations. Furthermore, genome-wide association studies on psychiatric disorders consistently implicate neuronal biology, whereas neurological diseases are associated with diverse neurobiological processes. Together, this study elucidates the genetic relationship between complex neurological and psychiatric disorders, indicating a larger degree of genetic pleiotropy than previously recognized. The findings have implications for disease classification, precision medicine and clinical practice. Genome-wide association studies Neurological disorders Psychiatric disorders biology
