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

Artikel i vetenskaplig tidskrift
Författare 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
Publicerad i Human molecular genetics
Volym 25
Nummer/häfte 15
Sidor 3383-94
ISSN 1460-2083
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor 3383-94
Språk en
Länkar dx.doi.org/10.1093/hmg/ddw181
Ämneskategorier Klinisk medicin, Psykiatri

Sammanfattning

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 within ERBB2 (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.

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