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

Hou, L. and Bergen, S. E. and Akula, N. and Song, J. and Hultman, C. M. and Landen, M. and Adli, M. and Alda, M. and Ardau, R. and Arias, B. and Aubry, J. M. and Backlund, L. and Badner, J. A. and Barrett, T. B. and Bauer, M. and Baune, B. T. and Bellivier, F. and Benabarre, A. and Bengesser, S. and Berrettini, W. H. and Bhattacharjee, A. K. and Biernacka, J. M. and Birner, A. and Bloss, C. S. and Brichant-Petitjean, C. and Bui, E. T. and Byerley, W. and Cervantes, P. and Chillotti, C. and Cichon, S. and Colom, F. and Coryell, W. and Craig, D. W. and Cruceanu, C. and Czerski, P. M. and Davis, T. and Dayer, A. and Degenhardt, F. and Del Zompo, M. and DePaulo, J. R. and Edenberg, H. J. and Etain, B. and Falkai, P. and Foroud, T. and Forstner, A. J. and Frisen, L. and Frye, M. A. and Fullerton, J. M. and Gard, S. and Garnham, J. S. and Gershon, E. S. and Goes, F. S. and Greenwood, T. A. and Grigoroiu-Serbanescu, M. and Hauser, J. and Heilbronner, U. and Heilmann-Heimbach, S. and Herms, S. and Hipolito, M. and Hitturlingappa, S. and Hoffmann, P. and Hofmann, A. and Jamain, S. and Jimenez, E. and Kahn, J. P. and Kassem, L. and Kelsoe, J. R. and Kittel-Schneider, S. and Kliwicki, S. and Koller, D. L. and Konig, B. and Lackner, N. and Laje, G. and Lang, M. and Lavebratt, C. and Lawson, W. B. and Leboyer, M. and Leckband, S. G. and Liu, C. and Maaser, A. and Mahon, P. B. and Maier, W. and Maj, M. and Manchia, M. and Martinsson, L. and McCarthy, M. J. and McElroy, S. L. and McInnis, M. G. and McKinney, R. and Mitchell, P. B. and Mitjans, M. and Mondimore, F. M. and Monteleone, P. and Muhleisen, T. W. and Nievergelt, C. M. and Nothen, M. M. and Novak, T. and Nurnberger, J. I. and Jr., and Nwulia, E. A. and Osby, U. and Pfennig, A. and Potash, J. B. and Propping, P. and Reif, A. and Reininghaus, E. and Rice, J. and Rietschel, M. and Rouleau, G. A. and Rybakowski, J. K. and Schalling, M. and Scheftner, W. A. and Schofield, P. R. and Schork, N. J. and Schulze, T. G. and Schumacher, J. and Schweizer, B. W. and Severino, G. and Shekhtman, T. and Shilling, P. D. and Simhandl, C. and Slaney, C. M. and Smith, E. N. and Squassina, A. and Stamm, T. and Stopkova, P. and Streit, F. and Strohmaier, J. and Szelinger, S. and Tighe, S. K. and Tortorella, A. and Turecki, G. and Vieta, E. and Volkert, J. and Witt, S. H. and Wright, A. and Zandi, P. P. and Zhang, P. and Zollner, S. and 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). pp. 3383-3394.

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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 approximately 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 x 10 - 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 x 10 - 9; OR = 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Apr 2019 16:20
Deposited On:09 Apr 2019 16:20

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