Author/Editor		Mullins, Niamh; Forstner, Andreas J; O'Connell, Kevin S; Coombes, Brandon; Tsermpini, Evangelia Erini
Title		Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Type		članek
Vol. and No.		Letnik 53, št. 6
Publication year		2021
Volume		str. 817-829
ISSN		1061-4036 - Nature genetics
Language		eng
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, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. 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.
Keywords		bipolarna motnja dedna duševna bolezen genetika bipolar disorder heritable mental illness genetics