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

Authors:
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 A 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

Hum Mol Genet 2016 08 21;25(15):3383-3394. Epub 2016 Jun 21.

Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA,

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   ; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10   ; 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.

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http://dx.doi.org/10.1093/hmg/ddw181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179929PMC
August 2016
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