Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
Authors: Hou Liping , Bergen Sarah E. , Akula Nirmala , Song Jie , Hultman Christina M. , Landén Mikael , Adli Mazda , Alda Martin , Ardau Raffaella , Arias Bárbara , Aubry Jean-Michel , Backlund Lena , Badner Judith A. , Barrett Thomas B. , Bauer Michael , Baune Bernhard T. , Bellivier Frank , Benabarre Antonio , Bengesser Susanne , Berrettini Wade H. , Bhattacharjee Abesh Kumar , Biernacka Joanna M. , Birner Armin , Bloss Cinnamon S. , Brichant-Petitjean Clara , Bui Elise T. , Byerley William , Cervantes Pablo , Chillotti Caterina , Cichon Sven , Colom Francesc , Coryell William , Craig David W. , Cruceanu Cristiana , Czerski Piotr M. , Davis Tony , Dayer Alexandre , Degenhardt Franziska , Del Zompo Maria , DePaulo J. Raymond , Edenberg Howard J. , Étain Bruno , Falkai Peter , Foroud Tatiana , Forstner Andreas J. , Frisén Louise , Frye Mark A. , Fullerton Janice M. , Gard Sébastien , Garnham Julie S. , Gershon Elliot S. , Goes Fernando S. , Greenwood Tiffany A. , Grigoroiu-Serbanescu Maria , Hauser Joanna , Heilbronner Urs , Heilmann-Heimbach Stefanie , Herms Stefan , Hipolito Maria , Hitturlingappa Shashi , Hoffmann Per , Hofmann Andrea , Jamain Stephane , Jiménez Esther , Kahn Jean-Pierre , Kassem Layla , Kelsoe John R. , Kittel-Schneider Sarah , Kliwicki Sebastian , Koller Daniel L. , König Barbara , Lackner Nina , Laje Gonzalo , Lang Maren , Lavebratt Catharina , Lawson William B. , Leboyer Marion , Leckband Susan G. , Liu Chunyu , Maaser Anna , Mahon Pamela B. , Maier Wolfgang , Maj Mario , Manchia Mirko , Martinsson Lina , McCarthy Michael J. , McElroy Susan L. , McInnis Melvin G. , McKinney Rebecca , Mitchell Philip B. , Mitjans Marina , Mondimore Francis M. , Monteleone Palmiero , Mühleisen Thomas W. , Nievergelt Caroline M. , Nöthen Markus M. , Novák Tomas , Nurnberger John I. , Nwulia Evaristus A. , Ösby Urban , Pfennig Andrea , Potash James B. , Propping Peter , Reif Andreas , Reininghaus Eva , Rice John , Rietschel Marcella , Rouleau Guy A. , Rybakowski Janusz K. , Schalling Martin , Scheftner William A. , Schofield Peter R. , Schork Nicholas J. , Schulze Thomas G. , Schumacher Johannes , Schweizer Barbara W. , Severino Giovanni , Shekhtman Tatyana , Shilling Paul D. , Simhandl Christian , Slaney Claire M. , Smith Erin N. , Squassina Alessio , Stamm Thomas , Stopkova Pavla , Streit Fabian , Strohmaier Jana , Szelinger Szabolcs , Tighe Sarah K. , Tortorella Alfonso , Turecki Gustavo , Vieta Eduard , Volkert Julia , Witt Stephanie H. , Wright Adam , Zandi Peter P. , Zhang Peng , Zollner Sebastian , McMahon Francis J. 
Published: March 2016

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 withinERBB2(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.