TY - JOUR
T1 - Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
AU - HUNT All-In Psychiatry
AU - Mullins, Niamh
AU - Forstner, Andreas J.
AU - O’Connell, Kevin S.
AU - Coombes, Brandon
AU - Coleman, Jonathan R.I.
AU - Qiao, Zhen
AU - Als, Thomas D.
AU - Bigdeli, Tim B.
AU - Børte, Sigrid
AU - Bryois, Julien
AU - Charney, Alexander W.
AU - Drange, Ole Kristian
AU - Gandal, Michael J.
AU - Hagenaars, Saskia P.
AU - Ikeda, Masashi
AU - Kamitaki, Nolan
AU - Kim, Minsoo
AU - Krebs, Kristi
AU - Panagiotaropoulou, Georgia
AU - Schilder, Brian M.
AU - Sloofman, Laura G.
AU - Steinberg, Stacy
AU - Trubetskoy, Vassily
AU - Winsvold, Bendik S.
AU - Won, Hong Hee
AU - Abramova, Liliya
AU - Adorjan, Kristina
AU - Agerbo, Esben
AU - Al Eissa, Mariam
AU - Albani, Diego
AU - Alliey-Rodriguez, Ney
AU - Anjorin, Adebayo
AU - Antilla, Verneri
AU - Antoniou, Anastasia
AU - Awasthi, Swapnil
AU - Baek, Ji Hyun
AU - Bækvad-Hansen, Marie
AU - Bass, Nicholas
AU - Bauer, Michael
AU - Beins, Eva C.
AU - Bergen, Sarah E.
AU - Birner, Armin
AU - Bøcker Pedersen, Carsten
AU - Bøen, Erlend
AU - Boks, Marco P.
AU - Bosch, Rosa
AU - Brum, Murielle
AU - Brumpton, Ben M.
AU - Brunkhorst-Kanaan, Nathalie
AU - Stein, Dan J.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107422437&partnerID=8YFLogxK
U2 - 10.1038/s41588-021-00857-4
DO - 10.1038/s41588-021-00857-4
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C2 - 34002096
AN - SCOPUS:85107422437
SN - 1061-4036
VL - 53
SP - 817
EP - 829
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -