학술논문
Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
Document Type
article
Author
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
Source
Human Molecular Genetics. 25(15)
Subject
Language
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 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.