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

Hum Mol Genet
Authors
Liping Hou
Sarah Bergen
Nirmala Akula
Jie Song
Christina Hultman
Mikael Landén
Mazda Adli
Martin Alda
Raffaella Ardau
Bárbara Arias
Jean-Michel Aubry
Lena Backlund
Judith Badner
Thomas Barrett
Michael Bauer
Bernhard Baune
Frank Bellivier
Antonio Benabarre
Susanne Bengesser
Wade Berrettini
Abesh Bhattacharjee
Joanna Biernacka
Armin Birner
Cinnamon Bloss
Clara Brichant-Petitjean
Elise Bui
William Byerley
Pablo Cervantes
Caterina Chillotti
Sven Cichon
Francesc Colom
William Coryell
David Craig
Cristiana Cruceanu
Piotr Czerski
Tony Davis
Alexandre Dayer
Franziska Degenhardt
Maria Del Zompo
J Raymond DePaulo
Howard Edenberg
Bruno Etain
Peter Falkai
Tatiana Foroud
Andreas Forstner
Louise Frisén
Mark Frye
Janice Fullerton
Sébastien Gard
Julie Garnham
Elliot Gershon
Fernando Goes
Tiffany Greenwood
Maria Grigoroiu-Serbanescu
Joanna Hauser
Urs Heilbronner
Stefanie Heilmann-Heimbach
Stefan Herms
Maria Hipolito
Shashi Hitturlingappa
Per Hoffmann
Andrea Hofmann
Stéphane Jamain
Esther Jiménez
Jean-Pierre Kahn
Layla Kassem
John Kelsoe
Sarah Kittel-Schneider
Sebastian Kliwicki
Daniel Koller
Barbara König
Nina Lackner
Gonzalo Laje
Maren Lang
Catharina Lavebratt
William Lawson
Marion Leboyer
Susan Leckband
Chunyu Liu
Anna Maaser
Pamela Mahon
Wolfgang Maier
Mario Maj
Mirko Manchia
Lina Martinsson
Michael McCarthy
Susan McElroy
Melvin McInnis
Rebecca McKinney
Philip Mitchell
Marina Mitjans
Francis Mondimore
Palmiero Monteleone
Thomas Mühleisen
Caroline Nievergelt
Markus Nöthen
Tomas Novák
John Nurnberger
Evaristus Nwulia
Urban Ösby
Andrea Pfennig
James Potash
Peter Propping
Andreas Reif
Eva Reininghaus
John Rice
Marcella Rietschel
Guy Rouleau
Janusz Rybakowski
Martin Schalling
William Scheftner
Peter Schofield
Nicholas Schork
Thomas Schulze
Johannes Schumacher
Barbara Schweizer
Giovanni Severino
Tatyana Shekhtman
Paul Shilling
Christian Simhandl
Claire Slaney
Erin Smith
Alessio Squassina
Thomas Stamm
Pavla Stopkova
Fabian Streit
Jana Strohmaier
Szabolcs Szelinger
Sarah Tighe
Alfonso Tortorella
Gustavo Turecki
Eduard Vieta
Julia Volkert
Stephanie Witt
Adam Wright
Peter Zandi
Peng Zhang
Sebastian Zollner
Francis McMahon
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.
Year of Publication
2016
Journal
Hum Mol Genet
Volume
25
Issue
15
Pages
3383-3394
Date Published
2016 Aug 01
ISSN
1460-2083
DOI
10.1093/hmg/ddw181
PubMed ID
27329760
PubMed Central ID
PMC5179929
Links
Grant list
R01 MH059556 / MH / NIMH NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
R01 MH059535 / MH / NIMH NIH HHS / United States
R01 MH101782 / MH / NIMH NIH HHS / United States
R01 MH059567 / MH / NIMH NIH HHS / United States
R01 MH059545 / MH / NIMH NIH HHS / United States
R01 MH101810 / MH / NIMH NIH HHS / United States
R01 MH101819 / MH / NIMH NIH HHS / United States
P01 CA089392 / CA / NCI NIH HHS / United States
R01 DA033684 / DA / NIDA NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
R01 MH059548 / MH / NIMH NIH HHS / United States
R01 MH059534 / MH / NIMH NIH HHS / United States
R01 MH059533 / MH / NIMH NIH HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
K02 DA021237 / DA / NIDA NIH HHS / United States
R01 MH101820 / MH / NIMH NIH HHS / United States
R01 MH101825 / MH / NIMH NIH HHS / United States
R01 MH090948 / MH / NIMH NIH HHS / United States
R01 MH090941 / MH / NIMH NIH HHS / United States
Z01 MH002810 / MH / NIMH NIH HHS / United States
R01 MH101822 / MH / NIMH NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
R01 MH059553 / MH / NIMH NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
R01 MH060068 / MH / NIMH NIH HHS / United States

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