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Tier 3 — Observational / field trialPeer-reviewed

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

Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon J. Coombes, Jonathan R. I. Coleman, Zhen Qiao, Thomas D. Als, Tim B. Bigdeli, Sigrid Børte, Julien Bryois, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Minsoo Kim, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura Sloofman, Stacy Steinberg, Vassily Trubetskoy, Bendik S. Winsvold, Hong‐Hee Won, Liliya Abramova, Kristina Adorjan, Esben Agerbo, Mariam Al Eissa, Diego Albani, Ney Alliey‐Rodriguez, Adebayo Anjorin, Verneri Antilla, Anastasia Antoniou, Swapnil Awasthi, Ji Hyun Baek, Marie Bækvad‐Hansen, Nicholas Bass, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, Rosa Bosch, Murielle Brum, Ben Brumpton, Nathalie Brunkhorst-Kanaan, Monika Budde, Jonas Bybjerg‐Grauholm, William Byerley, Murray J. Cairns, Miguel Casas, Pablo Cervantes, Toni‐Kim Clarke, Cristiana Cruceanu, Alfredo B. Cuéllar‐Barboza, Julie M. Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Franziska Degenhardt, Srdjan Djurovic, Amanda Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, Valentina Escott‐Price, I. Nicol Ferrier, Alessia Fiorentino, Tatiana Foroud, Liz Forty, Josef Frank, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Joel Gelernter, Marianne Giørtz Pedersen, Ian R. Gizer, Scott D. Gordon, Katherine Gordon‐Smith, Tiffany A. Greenwood, Jakob Grove, José Guzmán‐Parra, Kyooseob Ha, Magnús Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Stefan Herms, Per Hoffmann, Peter Holmans, Laura M. Huckins, Stéphane Jamain, Jessica Johnson, János Kálmán

Nature Genetics · 2021

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Summary

This large-scale genome-wide association study of over 40,000 bipolar disorder cases identified 64 associated genomic loci and implicated 15 genes as potential druggable targets, including HTR6, MCHR1, DCLK3 and FURIN. The findings reveal enrichment of risk alleles in synaptic signalling and genes expressed in the prefrontal cortex and hippocampus, with significant overlap with targets of existing antipsychotics and other psychiatric medications. The work advances understanding of bipolar disorder's biological aetiology and provides leads for therapeutic development and functional follow-up studies.

UK applicability

These genetic findings have potential relevance to UK psychiatric research and clinical practice, particularly in understanding biological mechanisms of bipolar disorder across European ancestry populations. However, direct application requires validation in diverse populations and integration with UK healthcare systems and treatment pathways.

Key measures

Genomic loci associated with bipolar disorder; gene expression correlation; enrichment in synaptic signalling pathways; genetic correlation between bipolar disorder type I and II

Outcomes reported

The study identified 64 genomic loci associated with bipolar disorder through analysis of 41,917 cases and 371,549 controls of European ancestry. Risk alleles were enriched in synaptic signalling pathways and brain-expressed genes, with 15 genes robustly implicated via gene expression analysis as potential druggable targets.

Theme
General food systems / other
Subject
Other / interdisciplinary
Study type
Research
Study design
Genome-wide association study (GWAS)
Source type
Peer-reviewed study
Status
Published
Geography
Europe
System type
Human clinical
DOI
10.1038/s41588-021-00857-4
Catalogue ID
SNmohdwgm4-8mj0nr

Topic tags

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