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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
By
Liping Hou,
Sarah E Bergen,
Nirmala Akula,
Jie Song,
Christina M Hultman,
Mikael Landén,
Mazda Adli,
Martin Alda,
Raffaella Ardau,
Bárbara Arias,
Jean-Michel Aubry,
Lena Backlund,
Judith A Badner,
Thomas B Barrett,
Michael Bauer,
Bernhard T. Baune,
Frank Bellivier,
Antonio Benabarre,
Susanne Bengesser,
Wade H Berrettini,
Abesh Kumar Bhattacharjee,
Joanna M. Biernacka,
Armin Birner,
Cinnamon S Bloss,
Clara Brichant-Petitjean,
Elise T Bui,
William Byerley,
Pablo Cervantes,
Caterina Chillotti,
Sven Cichon,
Francesc Colom,
William Coryell,
David W Craig,
Cristiana Cruceanu,
Piotr M. Czerski,
Tony Davis,
Alexandre Dayer,
Franziska Degenhardt,
Maria Del Zompo,
J. Raymond DePaulo,
Howard J Edenberg,
Bruno Étain,
Peter Falkai,
Tatiana Foroud,
Andreas J. Forstner,
Louise Frisén,
Mark Frye,
Janice M. Fullerton,
Sébastien Gard,
Julie S Garnham,
Elliot S. Gershon,
Fernando S. Goes,
Tiffany A Greenwood,
Maria Grigoroiu-Serbanescu,
Joanna Hauser,
Urs Heilbronner,
Stefanie Heilmann-Heimbach,
Stefan Herms,
Maria Hipolito,
Shashi Hitturlingappa,
Per Hoffmann,
Andrea Hofmann,
Stephane Jamain,
Esther Jiménez,
Jean-Pierre Kahn,
Layla Kassem,
John R Kelsoe,
Sarah Kittel-Schneider,
Sebastian Kliwicki,
Daniel L Koller,
Barbara König,
Nina Lackner,
Gonzalo Laje,
Maren Lang,
Catharina Lavebratt,
William B Lawson,
Marion Leboyer,
Susan G Leckband,
Chunyu Liu,
Anna Maaser,
Pamela B Mahon,
Wolfgang Maier,
Mario Maj,
Mirko Manchia,
Lina Martinsson,
Michael J. McCarthy,
Susan L McElroy,
Melvin G McInnis,
Rebecca McKinney,
Philip B Mitchell,
Marina Mitjans,
Francis M Mondimore,
Palmiero Monteleone,
Thomas W. Mühleisen,
Caroline M Nievergelt,
Markus M. Nöthen,
Tomas Novák,
John I. Nurnberger,
Evaristus A Nwulia,
Urban Ösby,
Andrea Pfennig,
James B. Potash,
Peter Propping,
Andreas Reif,
Eva Reininghaus,
John Rice,
Marcella Rietschel,
Guy A Rouleau,
Janusz K Rybakowski,
Martin Schalling,
William A Scheftner,
Peter R. Schofield,
Nicholas J. Schork,
Thomas G. Schulze,
Johannes Schumacher,
Barbara W Schweizer,
Giovanni Severino,
Tatyana Shekhtman,
Paul D Shilling,
Christian Simhandl,
Claire M Slaney,
Erin N. Smith,
Alessio Squassina,
Thomas Stamm,
Pavla Stopkova,
Fabian Streit,
Jana Strohmaier,
Szabolcs Szelinger,
Sarah K Tighe,
Alfonso Tortorella,
Gustavo Turecki,
Eduard Vieta,
Julia Volkert,
Stephanie H. Witt,
Adam Wright,
Peter P Zandi,
Peng Zhang,
Sebastian Zollner,
Francis J. McMahon
Posted 22 Mar 2016
bioRxiv DOI: 10.1101/044412
(published DOI: 10.1093/hmg/ddw181)
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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