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000892948 0247_ $$2doi$$a10.1038/s41588-021-00857-4
000892948 0247_ $$2pmid$$apmid:34002096
000892948 0247_ $$2ISSN$$a1061-4036
000892948 0247_ $$2ISSN$$a1546-1718
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000892948 037__ $$aFZJ-2021-02447
000892948 041__ $$aEnglish
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000892948 1001_ $$0P:(DE-HGF)0$$aMullins, Niamh$$b0$$eCorresponding author
000892948 245__ $$aGenome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.
000892948 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2021
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000892948 520__ $$aBipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
000892948 536__ $$0G:(DE-HGF)POF4-525$$a525 - Decoding Brain Organization and Dysfunction (POF4-525)$$cPOF4-525$$fPOF IV$$x0
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