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

Authors:
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

Nat Genet 2019 05 1;51(5):793-803. Epub 2019 May 1.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10) 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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Source
http://www.nature.com/articles/s41588-019-0397-8
Publisher Site
http://dx.doi.org/10.1038/s41588-019-0397-8DOI Listing
May 2019
9 Reads
29.352 Impact Factor

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References

(Supplied by CrossRef)
Article in Bipolar Disord.
AJ Ferrari et al.
Bipolar Disord. 2016
Article in Lancet
P Lichtenstein et al.
Lancet 2009
Article in J. Affect. Disord.
J Edvardsen et al.
J. Affect. Disord. 2008
Article in Arch. Gen. Psychiatry
P McGuffin et al.
Arch. Gen. Psychiatry 2003
Article in Br. J. Psychiatry
N Craddock et al.
Br. J. Psychiatry 2010
Article in Nat. Genet.
SH Lee et al.
Nat. Genet. 2013
Article in Nat. Genet.
P Sklar et al.
Nat. Genet. 2011
Article in Mol. Psychiatry
AE Baum et al.
Mol. Psychiatry 2008
Article in Transl. Psychiatry
AW Charney et al.
Transl. Psychiatry 2017
Article in Mol. Psychiatry
DT Chen et al.
Mol. Psychiatry 2013

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