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Genome-wide association study of over 40,000 bipolar disorder cases provides novel biological insights

Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, Gordon-Smith, Katherine ORCID: https://orcid.org/0000-0003-4083-1143 and Perry, Amy ORCID: https://orcid.org/0000-0002-9381-6636 (2021) Genome-wide association study of over 40,000 bipolar disorder cases provides novel biological insights. Nature Genetics. ISSN Print: 1061-4036 Online: 1546-1718

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Abstract

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD 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 eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Item Type: Article
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Uncontrolled Discrete Keywords: Bipolar disorder, Genome-Wide Association Study, GWAS, biological etiology
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Depositing User: Katherine Gordon-Smith
Date Deposited: 18 Mar 2021 08:10
Last Modified: 18 May 2021 08:08
URI: https://eprints.worc.ac.uk/id/eprint/10304

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