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Genome-wide association study identifies 30 loci associated with bipolar disorder.

Artikel i vetenskaplig tidskrift
Författare Eli A Stahl
Gerome Breen
Andreas J Forstner
Andrew McQuillin
Stephan Ripke
Vassily Trubetskoy
Manuel Mattheisen
Yunpeng Wang
Jonathan R I Coleman
Héléna A Gaspar
Christiaan A de Leeuw
Stacy Steinberg
Jennifer M Whitehead Pavlides
Maciej Trzaskowski
Enda M Byrne
Tune H Pers
Peter A Holmans
Alexander L Richards
Liam Abbott
Esben Agerbo
Huda Akil
Diego Albani
Ney Alliey-Rodriguez
Thomas D Als
Adebayo Anjorin
Verneri Antilla
Swapnil Awasthi
Judith A Badner
Marie Bækvad-Hansen
Jack D Barchas
Nicholas Bass
Michael Bauer
Richard Belliveau
Sarah E Bergen
Carsten Bøcker Pedersen
Erlend Bøen
Marco P Boks
James Boocock
Monika Budde
William Bunney
Margit Burmeister
Jonas Bybjerg-Grauholm
William Byerley
Miquel Casas
Felecia Cerrato
Pablo Cervantes
Kimberly Chambert
Alexander W Charney
Danfeng Chen
Claire Churchhouse
Toni-Kim Clarke
William Coryell
David W Craig
Cristiana Cruceanu
David Curtis
Piotr M Czerski
Anders M Dale
Simone de Jong
Franziska Degenhardt
Jurgen Del-Favero
J Raymond DePaulo
Srdjan Djurovic
Amanda L Dobbyn
Ashley Dumont
Torbjørn Elvsåshagen
Valentina Escott-Price
Chun Chieh Fan
Sascha B Fischer
Matthew Flickinger
Tatiana M Foroud
Liz Forty
Josef Frank
Christine Fraser
Nelson B Freimer
Louise Frisén
Katrin Gade
Diane Gage
Julie Garnham
Claudia Giambartolomei
Marianne Giørtz Pedersen
Jaqueline Goldstein
Scott D Gordon
Katherine Gordon-Smith
Elaine K Green
Melissa J Green
Tiffany A Greenwood
Jakob Grove
Weihua Guan
José Guzman-Parra
Marian L Hamshere
Martin Hautzinger
Urs Heilbronner
Stefan Herms
Maria Hipolito
Per Hoffmann
Dominic Holland
Laura Huckins
Stéphane Jamain
Jessica S Johnson
Anders Juréus
Radhika Kandaswamy
Robert Karlsson
James L Kennedy
Sarah Kittel-Schneider
James A Knowles
Manolis Kogevinas
Anna C Koller
Ralph Kupka
Catharina Lavebratt
Jacob Lawrence
William B Lawson
Markus Leber
Phil H Lee
Shawn E Levy
Jun Z Li
Chunyu Liu
Susanne Lucae
Anna Maaser
Donald J MacIntyre
Pamela B Mahon
Wolfgang Maier
Lina Martinsson
Steve McCarroll
Peter McGuffin
Melvin G McInnis
James D McKay
Helena Medeiros
Sarah E Medland
Fan Meng
Lili Milani
Grant W Montgomery
Derek W Morris
Thomas W Mühleisen
Niamh Mullins
Hoang Nguyen
Caroline M Nievergelt
Annelie Nordin Adolfsson
Evaristus A Nwulia
Claire O'Donovan
Loes M Olde Loohuis
Anil P S Ori
Lilijana Oruc
Urban Ösby
Roy H Perlis
Amy Perry
Andrea Pfennig
James B Potash
Shaun M Purcell
Eline J Regeer
Andreas Reif
Céline S Reinbold
John P Rice
Fabio Rivas
Margarita Rivera
Panos Roussos
Douglas M Ruderfer
Euijung Ryu
Cristina Sánchez-Mora
Alan F Schatzberg
William A Scheftner
Nicholas J Schork
Cynthia Shannon Weickert
Tatyana Shehktman
Paul D Shilling
Engilbert Sigurdsson
Claire Slaney
Olav B Smeland
Janet L Sobell
Christine Søholm Hansen
Anne T Spijker
David St Clair
Michael Steffens
John S Strauss
Fabian Streit
Jana Strohmaier
Szabolcs Szelinger
Robert C Thompson
Thorgeir E Thorgeirsson
Jens Treutlein
Helmut Vedder
Weiqing Wang
Stanley J Watson
Thomas W Weickert
Stephanie H Witt
Simon Xi
Wei Xu
Allan H Young
Peter Zandi
Peng Zhang
Sebastian Zöllner
Rolf Adolfsson
Ingrid Agartz
Martin Alda
Lena Backlund
Bernhard T Baune
Frank Bellivier
Wade H Berrettini
Joanna M Biernacka
Douglas H R Blackwood
Michael Boehnke
Anders D Børglum
Aiden Corvin
Nicholas Craddock
Mark J Daly
Udo Dannlowski
Tõnu Esko
Bruno Etain
Mark Frye
Janice M Fullerton
Elliot S Gershon
Michael Gill
Fernando Goes
Maria Grigoroiu-Serbanescu
Joanna Hauser
David M Hougaard
Christina M Hultman
Ian Jones
Lisa A Jones
René S Kahn
George Kirov
Mikael Landén
Marion Leboyer
Cathryn M Lewis
Qingqin S Li
Jolanta Lissowska
Nicholas G Martin
Fermin Mayoral
Susan L McElroy
Andrew M McIntosh
Francis J McMahon
Ingrid Melle
Andres Metspalu
Philip B Mitchell
Gunnar Morken
Ole Mors
Preben Bo Mortensen
Bertram Müller-Myhsok
Richard M Myers
Benjamin M Neale
Vishwajit Nimgaonkar
Merete Nordentoft
Markus M Nöthen
Michael C O'Donovan
Ketil J Oedegaard
Michael J Owen
Sara A Paciga
Carlos Pato
Michele T Pato
Danielle Posthuma
Josep Antoni Ramos-Quiroga
Marta Ribasés
Marcella Rietschel
Guy A Rouleau
Martin Schalling
Peter R Schofield
Thomas G Schulze
Alessandro Serretti
Jordan W Smoller
Hreinn Stefansson
Kari Stefansson
Eystein Stordal
Patrick F Sullivan
Gustavo Turecki
Arne E Vaaler
Eduard Vieta
John B Vincent
Thomas Werge
John I Nurnberger
Naomi R Wray
Arianna Di Florio
Howard J Edenberg
Sven Cichon
Roel A Ophoff
Laura J Scott
Ole A Andreassen
John Kelsoe
Pamela Sklar
Publicerad i Nature genetics
Volym 51
Nummer/häfte 5
Sidor 793-803
ISSN 1546-1718
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 793-803
Språk en
Länkar dx.doi.org/10.1038/s41588-019-0397-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Psykiatri

Sammanfattning

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

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