Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology



Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Borte, Sigrid, Bryois, Julien
et al (show 305 more authors) (2021) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. NATURE GENETICS, 53 (6). 817-+.

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Abstract

Bipolar 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.

Item Type: Article
Uncontrolled Keywords: HUNT All-In Psychiatry, Chromosomes, Human, Humans, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Bipolar Disorder, Major Histocompatibility Complex, Multifactorial Inheritance, Phenotype, Quantitative Trait Loci, Genome, Human, Genome-Wide Association Study
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 21 Dec 2021 16:23
Last Modified: 18 Jan 2023 21:18
DOI: 10.1038/s41588-021-00857-4
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3145820