Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Hou L, Bergen SE, Akula N, Song J, Hultman CM, Landén M, Adli M, Alda M, Ardau R, Arias B, Aubry JM, Backlund L, Badner JA, Barrett TB, Bauer M, Baune BT, Bellivier F, Benabarre A, Bengesser S, Berrettini WH, Bhattacharjee AK, Biernacka JM, Birner A, Bloss CS, Brichant-Petitjean C, Bui ET, Byerley W, Cervantes P, Chillotti C, Cichon S, Colom F, Coryell W, Craig DW, Cruceanu C, Czerski PM, Davis T, Dayer A, Degenhardt F, Del Zompo M, DePaulo JR, Edenberg HJ, Étain B, Falkai P, Foroud T, Forstner AJ, Frisén L, Frye MA, Fullerton JM, Gard S, Garnham JS, Gershon ES, Goes FS, Greenwood TA, Grigoroiu-Serbanescu M, Hauser J, Heilbronner U, Heilmann-Heimbach S, Herms S, Hipolito M, Hitturlingappa S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kelsoe JR, Kittel-Schneider S, Kliwicki S, Koller DL, König B, Lackner N, Laje G, Lang M, Lavebratt C, Lawson WB, Leboyer M, Leckband SG, Liu C, Maaser A, Mahon PB, Maier W, Maj M, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, McInnis MG, McKinney R, Mitchell PB, Mitjans M, Mondimore FM, Monteleone P, Mühleisen TW, Nievergelt CM, Nöthen MM, Novák T, Nurnberger JI, Nwulia EA, Ösby U, Pfennig A, Potash JB, Propping P, Reif A, Reininghaus E, Rice J, Rietschel M, Rouleau GA, Rybakowski JK, Schalling M, Scheftner WA, Schofield PR, Schork NJ, Schulze TG, Schumacher J, Schweizer BW, Severino G, Shekhtman T, Shilling PD, Simhandl C, Slaney CM, Smith EN, Squassina A, Stamm T, Stopkova P, Streit F, Strohmaier J, Szelinger S, Tighe SK, Tortorella A, Turecki G, Vieta E, Volkert J, Witt SH, Wright A, Zandi PP, Zhang P, Zollner S, McMahon FJ (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 25

Pages Range: 3383-3394

Journal Issue: 15

DOI: 10.1093/hmg/ddw181

Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. 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 (OR)=1.12) and markers within ERBB2 (rs2517959, P= 4.53×10^-9; OR=1.13). No significant X-chromosome associations were detected and Xlinked 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.

Involved external institutions

Howard University Hospital (HUH) / Freedmen's Hospital United States (USA) (US) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) University of Chicago United States (USA) (US) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) University of Iowa United States (USA) (US) Johns Hopkins Hospital United States (USA) (US) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Medizinische Universität Graz Austria (AT) Washington University in St. Louis United States (USA) (US) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) University of Michigan United States (USA) (US) Dalhousie University Canada (CA) Scripps Research Institute (TSRI) United States (USA) (US) National Institute of Mental Health Information Resource Center United States (USA) (US) Università degli Studi di Cagliari Italy (IT) Charité - Universitätsmedizin Berlin Germany (DE) National Institute of Mental Health (NIMH) / Národní ústav duševního zdraví (NUDZ) Czech Republic (CZ) Ruprecht-Karls-Universität Heidelberg Germany (DE) Translational Genomics Research Institute (TGen) United States (USA) (US) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Klinikum der Universität München (LMU Klinikum) Germany (DE) Douglas Mental Health University Institute Canada (CA) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Johns Hopkins University (JHU) United States (USA) (US) Mondor Institute of Biomedical Research (IMRB) France (FR) VA San Diego Healthcare System United States (USA) (US) University of Iowa Hospitals and Clinics (UIHC) United States (USA) (US) University of Pennsylvania (UPenn) United States (USA) (US) Mayo Clinic United States (USA) (US) Indiana University – Purdue University Indianapolis United States (USA) (US) Université Paris Cité France (FR) Neuroscience Research Australia NeuRA Australia (AU) Centre Hospitalier Charles Perrens (CHCP) France (FR) University of Illinois at Chicago United States (USA) (US) Rush University United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Montreal Neurological Institute and Hospital (MNI, The Neuro) Canada (CA) BIPOLAR Zentrum Wiener Neustadt Austria (AT) University of Adelaide Australia (AU) Paris-Est Créteil University / Université Paris-Est Créteil Val-de-Marne (UPEC) / Université Paris XII-Val-de-Marne / University Paris 12 Marne la Vallée France (FR) Université de Lorraine France (FR) Karolinska Institute Sweden (SE) University of Cincinnati United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Veterans Affairs Medical Center (VA Portland) United States (USA) (US)

How to cite

APA:

Hou, L., Bergen, S.E., Akula, N., Song, J., Hultman, C.M., Landén, M.,... McMahon, F.J. (2016). Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. Human Molecular Genetics, 25(15), 3383-3394. https://doi.org/10.1093/hmg/ddw181

MLA:

Hou, Liping, et al. "Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder." Human Molecular Genetics 25.15 (2016): 3383-3394.

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