TY  - JOUR
TI  - Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
AU  - Niamh Mullins
AU  - Andreas J. Forstner
AU  - Kevin S. O’Connell
AU  - Brandon J. Coombes
AU  - Jonathan R. I. Coleman
AU  - Zhen Qiao
AU  - Thomas D. Als
AU  - Tim B. Bigdeli
AU  - Sigrid Børte
AU  - Julien Bryois
AU  - Alexander W. Charney
AU  - Ole Kristian Drange
AU  - Michael J. Gandal
AU  - Saskia P. Hagenaars
AU  - Masashi Ikeda
AU  - Nolan Kamitaki
AU  - Minsoo Kim
AU  - Kristi Krebs
AU  - Georgia Panagiotaropoulou
AU  - Brian M. Schilder
AU  - Laura Sloofman
AU  - Stacy Steinberg
AU  - Vassily Trubetskoy
AU  - Bendik S. Winsvold
AU  - Hong‐Hee Won
AU  - Liliya Abramova
AU  - Kristina Adorjan
AU  - Esben Agerbo
AU  - Mariam Al Eissa
AU  - Diego Albani
AU  - Ney Alliey‐Rodriguez
AU  - Adebayo Anjorin
AU  - Verneri Antilla
AU  - Anastasia Antoniou
AU  - Swapnil Awasthi
AU  - Ji Hyun Baek
AU  - Marie Bækvad‐Hansen
AU  - Nicholas Bass
AU  - Michael Bauer
AU  - Eva C. Beins
AU  - Sarah E. Bergen
AU  - Armin Birner
AU  - Carsten Bøcker Pedersen
AU  - Erlend Bøen
AU  - Marco P. Boks
AU  - Rosa Bosch
AU  - Murielle Brum
AU  - Ben Brumpton
AU  - Nathalie Brunkhorst-Kanaan
AU  - Monika Budde
AU  - Jonas Bybjerg‐Grauholm
AU  - William Byerley
AU  - Murray J. Cairns
AU  - Miguel Casas
AU  - Pablo Cervantes
AU  - Toni‐Kim Clarke
AU  - Cristiana Cruceanu
AU  - Alfredo B. Cuéllar‐Barboza
AU  - Julie M. Cunningham
AU  - David Curtis
AU  - Piotr M. Czerski
AU  - Anders M. Dale
AU  - Nina Dalkner
AU  - Friederike S. David
AU  - Franziska Degenhardt
AU  - Srdjan Djurovic
AU  - Amanda Dobbyn
AU  - Athanassios Douzenis
AU  - Torbjørn Elvsåshagen
AU  - Valentina Escott‐Price
AU  - I. Nicol Ferrier
AU  - Alessia Fiorentino
AU  - Tatiana Foroud
AU  - Liz Forty
AU  - Josef Frank
AU  - Oleksandr Frei
AU  - Nelson B. Freimer
AU  - Louise Frisén
AU  - Katrin Gade
AU  - Julie Garnham
AU  - Joel Gelernter
AU  - Marianne Giørtz Pedersen
AU  - Ian R. Gizer
AU  - Scott D. Gordon
AU  - Katherine Gordon‐Smith
AU  - Tiffany A. Greenwood
AU  - Jakob Grove
AU  - José Guzmán‐Parra
AU  - Kyooseob Ha
AU  - Magnús Haraldsson
AU  - Martin Hautzinger
AU  - Urs Heilbronner
AU  - Dennis Hellgren
AU  - Stefan Herms
AU  - Per Hoffmann
AU  - Peter Holmans
AU  - Laura M. Huckins
AU  - Stéphane Jamain
AU  - Jessica Johnson
AU  - János Kálmán
PY  - 2021
JO  - Nature Genetics
DO  - 10.1038/s41588-021-00857-4
UR  - https://doi.org/10.1038/s41588-021-00857-4
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. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
ER  -