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Journal Articles Nature Genetics Year : 2021

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

Niamh Mullins , Andreas Forstner , Kevin O'Connell , Brandon Coombes , Jonathan Coleman , Zhen Qiao , Thomas Als , Tim Bigdeli , Sigrid Børte , Julien Bryois , Alexander Charney , Ole Kristian Drange , Michael Gandal , Saskia Hagenaars , Masashi Ikeda , Nolan Kamitaki , Minsoo Kim , Kristi Krebs , Georgia Panagiotaropoulou , Brian Schilder , Laura Sloofman , Stacy Steinberg , Vassily Trubetskoy , Bendik 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 Beins , Sarah Bergen , Armin Birner , Carsten Bøcker Pedersen , Erlend Bøen , Marco Boks , Rosa Bosch , Murielle Brum , Ben Brumpton , Nathalie Brunkhorst-Kanaan , Monika Budde , Jonas Bybjerg-Grauholm , William Byerley , Murray Cairns , Miquel Casas , Pablo Cervantes , Toni-Kim Clarke , Cristiana Cruceanu , Alfredo Cuellar-Barboza , Julie Cunningham , David Curtis , Piotr Czerski , Anders Dale , Nina Dalkner , Friederike 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 Freimer , Louise Frisén , Katrin Gade , Julie Garnham , Joel Gelernter , Marianne Giørtz Pedersen , Ian Gizer , Scott Gordon , Katherine Gordon-Smith , Tiffany Greenwood , Jakob Grove , José Guzman-Parra , Kyooseob Ha , Magnus Haraldsson , Martin Hautzinger , Urs Heilbronner , Dennis Hellgren , Stefan Herms , Per Hoffmann , Peter Holmans , Laura Huckins , Stéphane Jamain (1) , Jessica Johnson , Janos Kalman , Yoichiro Kamatani , James Kennedy , Sarah Kittel-Schneider , James Knowles , Manolis Kogevinas , Maria Koromina , Thorsten Kranz , Henry Kranzler , Michiaki Kubo , Ralph Kupka , Steven Kushner , Catharina Lavebratt , Jacob Lawrence , Markus Leber , Heon-Jeong Lee , Phil Lee , Shawn Levy , Catrin Lewis , Calwing Liao , Susanne Lucae , Martin Lundberg , Donald Macintyre , Sigurdur Magnusson , Wolfgang Maier , Adam Maihofer , Dolores Malaspina , Eirini Maratou , Lina Martinsson , Manuel Mattheisen , Steven Mccarroll , Nathaniel Mcgregor , Peter Mcguffin , James Mckay (2) , Helena Medeiros , Sarah Medland , Vincent Millischer , Grant Montgomery , Jennifer Moran , Derek Morris , Thomas Mühleisen , Niamh O'Brien , Claire O'Donovan , Loes Olde Loohuis , Lilijana Oruc , Sergi Papiol , Antonio Pardiñas , Amy Perry , Andrea Pfennig , Evgenia Porichi , James Potash , Digby Quested , Towfique Raj , Mark Rapaport , J Raymond Depaulo , Eline Regeer , John Rice , Fabio Rivas , Margarita Rivera , Julian Roth , Panos Roussos , Douglas Ruderfer , Cristina Sánchez-Mora , Eva Schulte , Fanny Senner , Sally Sharp , Paul Shilling , Engilbert Sigurdsson , Lea Sirignano , Claire Slaney , Olav Smeland , Daniel Smith , Janet Sobell , Christine Søholm Hansen , Maria Soler Artigas , Anne Spijker , Dan Stein , John Strauss , Beata Świątkowska , Chikashi Terao , Thorgeir Thorgeirsson , Claudio Toma , Paul Tooney , Evangelia-Eirini Tsermpini , Marquis Vawter , Helmut Vedder , James Walters , Stephanie Witt , Simon Xi , Wei Xu , Jessica Mei Kay Yang , Allan Young , Hannah Young , Peter Zandi , Hang Zhou , Lea Zillich , Rolf Adolfsson , Ingrid Agartz , Martin Alda , Lars Alfredsson , Gulja Babadjanova , Lena Backlund , Bernhard Baune , Frank Bellivier (3, 4) , Susanne Bengesser , Wade Berrettini , Douglas Blackwood , Michael Boehnke , Anders Børglum , Gerome Breen , Vaughan Carr , Stanley Catts , Aiden Corvin , Nicholas Craddock , Udo Dannlowski , Dimitris Dikeos , Tõnu Esko , Bruno Etain (3, 4) , Panagiotis Ferentinos , Mark Frye , Janice Fullerton , Micha Gawlik , Elliot Gershon , Fernando Goes , Melissa Green , Maria Grigoroiu-Serbanescu , Joanna Hauser , Frans Henskens , Jan Hillert , Kyung Sue Hong , David Hougaard , Christina Hultman , Kristian Hveem , Nakao Iwata , Assen Jablensky , Ian Jones , Lisa Jones , René Kahn , John Kelsoe , George Kirov , Mikael Landén , Marion Leboyer (1) , Cathryn Lewis , Qingqin Li , Jolanta Lissowska , Christine Lochner , Carmel Loughland , Nicholas Martin , Carol Mathews , Fermin Mayoral , Susan Mcelroy , Andrew McIntosh , Francis Mcmahon , Ingrid Melle , Patricia Michie , Lili Milani , Philip Mitchell , Gunnar Morken , Ole Mors , Preben Bo Mortensen , Bryan Mowry , Bertram Müller-Myhsok , Richard Myers , Benjamin Neale , Caroline Nievergelt , Merete Nordentoft , Markus Nöthen , Michael O'Donovan , Ketil Oedegaard , Tomas Olsson , Michael Owen , Sara Paciga , Chris Pantelis , Carlos Pato , Michele Pato , George Patrinos , Roy Perlis , Danielle Posthuma , Josep Antoni Ramos-Quiroga , Andreas Reif , Eva Reininghaus , Marta Ribasés , Marcella Rietschel , Stephan Ripke , Guy Rouleau , Takeo Saito , Ulrich Schall , Martin Schalling , Peter Schofield , Thomas Schulze , Laura Scott , Rodney Scott , Alessandro Serretti , Cynthia Shannon Weickert , Jordan Smoller , Hreinn Stefansson , Kari Stefansson , Eystein Stordal , Fabian Streit , Patrick Sullivan , Gustavo Turecki , Arne Vaaler , Eduard Vieta , John Vincent , Irwin Waldman , Thomas Weickert , Thomas Werge , Naomi Wray , John-Anker Zwart , Joanna Biernacka , John Nurnberger , Sven Cichon , Howard Edenberg , Eli Stahl , Andrew Mcquillin , Arianna Di Florio , Roel Ophoff , Ole Andreassen , Kevin O’connell , I. Nicol Ferrier , Niamh O’brien , Claire O’donovan , J. Raymond Depaulo , Michael O’donovan
Niamh Mullins
Andreas Forstner
  • Function : Author
Kevin O'Connell
  • Function : Author
Brandon Coombes
  • Function : Author
Jonathan Coleman
  • Function : Author
Zhen Qiao
  • Function : Author
Thomas Als
  • Function : Author
Tim Bigdeli
  • Function : Author
Sigrid Børte
  • Function : Author
Julien Bryois
  • Function : Author
Alexander Charney
  • Function : Author
Ole Kristian Drange
  • Function : Author
Michael Gandal
  • Function : Author
Saskia Hagenaars
  • Function : Author
Masashi Ikeda
  • Function : Author
Nolan Kamitaki
  • Function : Author
Minsoo Kim
  • Function : Author
Kristi Krebs
  • Function : Author
Georgia Panagiotaropoulou
  • Function : Author
Brian Schilder
  • Function : Author
Laura Sloofman
  • Function : Author
Stacy Steinberg
  • Function : Author
Vassily Trubetskoy
  • Function : Author
Bendik Winsvold
  • Function : Author
Hong-Hee Won
  • Function : Author
Liliya Abramova
  • Function : Author
Kristina Adorjan
  • Function : Author
Esben Agerbo
  • Function : Author
Mariam Al Eissa
  • Function : Author
Diego Albani
  • Function : Author
Ney Alliey-Rodriguez
  • Function : Author
Adebayo Anjorin
  • Function : Author
Verneri Antilla
  • Function : Author
Anastasia Antoniou
  • Function : Author
Swapnil Awasthi
  • Function : Author
Ji Hyun Baek
  • Function : Author
Marie Bækvad-Hansen
  • Function : Author
Nicholas Bass
  • Function : Author
Michael Bauer
  • Function : Author
Eva Beins
  • Function : Author
Sarah Bergen
  • Function : Author
Armin Birner
  • Function : Author
Carsten Bøcker Pedersen
  • Function : Author
Erlend Bøen
  • Function : Author
Marco Boks
  • Function : Author
Rosa Bosch
  • Function : Author
Murielle Brum
  • Function : Author
Ben Brumpton
  • Function : Author
Nathalie Brunkhorst-Kanaan
  • Function : Author
Monika Budde
  • Function : Author
Jonas Bybjerg-Grauholm
  • Function : Author
William Byerley
  • Function : Author
Murray Cairns
  • Function : Author
Miquel Casas
  • Function : Author
Pablo Cervantes
  • Function : Author
Toni-Kim Clarke
  • Function : Author
Cristiana Cruceanu
  • Function : Author
Alfredo Cuellar-Barboza
  • Function : Author
Julie Cunningham
  • Function : Author
David Curtis
  • Function : Author
Piotr Czerski
  • Function : Author
Anders Dale
  • Function : Author
Nina Dalkner
  • Function : Author
Friederike David
  • Function : Author
Franziska Degenhardt
  • Function : Author
Srdjan Djurovic
  • Function : Author
Amanda Dobbyn
  • Function : Author
Athanassios Douzenis
  • Function : Author
Torbjørn Elvsåshagen
  • Function : Author
Valentina Escott-Price
  • Function : Author
I Nicol Ferrier
  • Function : Author
Alessia Fiorentino
  • Function : Author
Tatiana Foroud
  • Function : Author
Liz Forty
  • Function : Author
Josef Frank
  • Function : Author
Oleksandr Frei
  • Function : Author
Nelson Freimer
  • Function : Author
Louise Frisén
  • Function : Author
Katrin Gade
  • Function : Author
Julie Garnham
  • Function : Author
Joel Gelernter
  • Function : Author
Marianne Giørtz Pedersen
  • Function : Author
Ian Gizer
  • Function : Author
Scott Gordon
  • Function : Author
Katherine Gordon-Smith
  • Function : Author
Tiffany Greenwood
  • Function : Author
Jakob Grove
  • Function : Author
José Guzman-Parra
  • Function : Author
Kyooseob Ha
  • Function : Author
Magnus Haraldsson
  • Function : Author
Martin Hautzinger
  • Function : Author
Urs Heilbronner
  • Function : Author
Dennis Hellgren
  • Function : Author
Stefan Herms
  • Function : Author
Per Hoffmann
  • Function : Author
Peter Holmans
  • Function : Author
Laura Huckins
  • Function : Author
Jessica Johnson
  • Function : Author
Janos Kalman
  • Function : Author
Yoichiro Kamatani
  • Function : Author
James Kennedy
  • Function : Author
Sarah Kittel-Schneider
  • Function : Author
James Knowles
  • Function : Author
Manolis Kogevinas
  • Function : Author
Maria Koromina
  • Function : Author
Thorsten Kranz
  • Function : Author
Henry Kranzler
  • Function : Author
Michiaki Kubo
  • Function : Author
Ralph Kupka
  • Function : Author
Steven Kushner
  • Function : Author
Catharina Lavebratt
  • Function : Author
Jacob Lawrence
  • Function : Author
Markus Leber
  • Function : Author
Heon-Jeong Lee
  • Function : Author
Phil Lee
  • Function : Author
Shawn Levy
  • Function : Author
Catrin Lewis
  • Function : Author
Calwing Liao
  • Function : Author
Susanne Lucae
  • Function : Author
Martin Lundberg
  • Function : Author
Donald Macintyre
  • Function : Author
Sigurdur Magnusson
  • Function : Author
Wolfgang Maier
  • Function : Author
Adam Maihofer
  • Function : Author
Dolores Malaspina
  • Function : Author
Eirini Maratou
  • Function : Author
Lina Martinsson
  • Function : Author
Manuel Mattheisen
  • Function : Author
Steven Mccarroll
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Nathaniel Mcgregor
  • Function : Author
Peter Mcguffin
  • Function : Author
Helena Medeiros
  • Function : Author
Sarah Medland
  • Function : Author
Vincent Millischer
  • Function : Author
Grant Montgomery
  • Function : Author
Jennifer Moran
  • Function : Author
Derek Morris
  • Function : Author
Thomas Mühleisen
  • Function : Author
Niamh O'Brien
  • Function : Author
Claire O'Donovan
  • Function : Author
Loes Olde Loohuis
  • Function : Author
Lilijana Oruc
  • Function : Author
Sergi Papiol
  • Function : Author
Antonio Pardiñas
  • Function : Author
Amy Perry
  • Function : Author
Andrea Pfennig
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Evgenia Porichi
  • Function : Author
James Potash
  • Function : Author
Digby Quested
  • Function : Author
Towfique Raj
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Mark Rapaport
  • Function : Author
J Raymond Depaulo
  • Function : Author
Eline Regeer
  • Function : Author
John Rice
  • Function : Author
Fabio Rivas
  • Function : Author
Margarita Rivera
  • Function : Author
Julian Roth
  • Function : Author
Panos Roussos
  • Function : Author
Douglas Ruderfer
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Cristina Sánchez-Mora
  • Function : Author
Eva Schulte
  • Function : Author
Fanny Senner
  • Function : Author
Sally Sharp
  • Function : Author
Paul Shilling
  • Function : Author
Engilbert Sigurdsson
  • Function : Author
Lea Sirignano
  • Function : Author
Claire Slaney
  • Function : Author
Olav Smeland
  • Function : Author
Daniel Smith
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Janet Sobell
  • Function : Author
Christine Søholm Hansen
  • Function : Author
Maria Soler Artigas
  • Function : Author
Anne Spijker
  • Function : Author
Dan Stein
  • Function : Author
John Strauss
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Beata Świątkowska
  • Function : Author
Chikashi Terao
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Thorgeir Thorgeirsson
  • Function : Author
Claudio Toma
  • Function : Author
Paul Tooney
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Evangelia-Eirini Tsermpini
  • Function : Author
Marquis Vawter
  • Function : Author
Helmut Vedder
  • Function : Author
James Walters
  • Function : Author
Stephanie Witt
  • Function : Author
Simon Xi
  • Function : Author
Wei Xu
  • Function : Author
Jessica Mei Kay Yang
  • Function : Author
Allan Young
  • Function : Author
Hannah Young
  • Function : Author
Peter Zandi
  • Function : Author
Hang Zhou
  • Function : Author
Lea Zillich
  • Function : Author
Rolf Adolfsson
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Ingrid Agartz
  • Function : Author
Martin Alda
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Lars Alfredsson
  • Function : Author
Gulja Babadjanova
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Lena Backlund
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Bernhard Baune
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Susanne Bengesser
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Wade Berrettini
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Douglas Blackwood
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Michael Boehnke
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Anders Børglum
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Gerome Breen
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Vaughan Carr
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Stanley Catts
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Aiden Corvin
  • Function : Author
Nicholas Craddock
  • Function : Author
Udo Dannlowski
  • Function : Author
Dimitris Dikeos
  • Function : Author
Tõnu Esko
  • Function : Author
Panagiotis Ferentinos
  • Function : Author
Mark Frye
  • Function : Author
Janice Fullerton
  • Function : Author
Micha Gawlik
  • Function : Author
Elliot Gershon
  • Function : Author
Fernando Goes
  • Function : Author
Melissa Green
  • Function : Author
Maria Grigoroiu-Serbanescu
  • Function : Author
Joanna Hauser
  • Function : Author
Frans Henskens
  • Function : Author
Jan Hillert
  • Function : Author
Kyung Sue Hong
  • Function : Author
David Hougaard
  • Function : Author
Christina Hultman
  • Function : Author
Kristian Hveem
  • Function : Author
Nakao Iwata
  • Function : Author
Assen Jablensky
  • Function : Author
Ian Jones
  • Function : Author
Lisa Jones
  • Function : Author
René Kahn
  • Function : Author
John Kelsoe
  • Function : Author
George Kirov
  • Function : Author
Mikael Landén
  • Function : Author
Cathryn Lewis
  • Function : Author
Qingqin Li
  • Function : Author
Jolanta Lissowska
  • Function : Author
Christine Lochner
  • Function : Author
Carmel Loughland
  • Function : Author
Nicholas Martin
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Carol Mathews
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Fermin Mayoral
  • Function : Author
Susan Mcelroy
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Andrew McIntosh
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Francis Mcmahon
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Ingrid Melle
  • Function : Author
Patricia Michie
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Lili Milani
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Philip Mitchell
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Gunnar Morken
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Ole Mors
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Preben Bo Mortensen
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Bryan Mowry
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Bertram Müller-Myhsok
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Richard Myers
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Benjamin Neale
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Caroline Nievergelt
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Merete Nordentoft
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Markus Nöthen
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Michael O'Donovan
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Ketil Oedegaard
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Tomas Olsson
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Michael Owen
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Sara Paciga
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Chris Pantelis
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Carlos Pato
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Michele Pato
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George Patrinos
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Roy Perlis
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Danielle Posthuma
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Josep Antoni Ramos-Quiroga
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Andreas Reif
  • Function : Author
Eva Reininghaus
  • Function : Author
Marta Ribasés
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Marcella Rietschel
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Stephan Ripke
  • Function : Author
Guy Rouleau
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Takeo Saito
  • Function : Author
Ulrich Schall
  • Function : Author
Martin Schalling
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Peter Schofield
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Thomas Schulze
  • Function : Author
Laura Scott
  • Function : Author
Rodney Scott
  • Function : Author
Alessandro Serretti
  • Function : Author
Cynthia Shannon Weickert
  • Function : Author
Jordan Smoller
  • Function : Author
Hreinn Stefansson
  • Function : Author
Kari Stefansson
  • Function : Author
Eystein Stordal
  • Function : Author
Fabian Streit
  • Function : Author
Patrick Sullivan
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Gustavo Turecki
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Arne Vaaler
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Eduard Vieta
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John Vincent
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Irwin Waldman
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Thomas Weickert
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Thomas Werge
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Naomi Wray
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John-Anker Zwart
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Joanna Biernacka
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John Nurnberger
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Sven Cichon
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Howard Edenberg
  • Function : Author
Eli Stahl
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Andrew Mcquillin
  • Function : Author
Arianna Di Florio
  • Function : Author
Roel Ophoff
  • Function : Author
Ole Andreassen
Kevin O’connell
  • Function : Author
I. Nicol Ferrier
  • Function : Author
Niamh O’brien
  • Function : Author
Claire O’donovan
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J. Raymond Depaulo
  • Function : Author
Michael O’donovan
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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.
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Dates and versions

inserm-03854548 , version 1 (08-04-2024)

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Niamh Mullins, Andreas Forstner, Kevin O'Connell, Brandon Coombes, Jonathan Coleman, et al.. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics, 2021, 53 (6), pp.817-829. ⟨10.1038/s41588-021-00857-4⟩. ⟨inserm-03854548⟩
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