Genome-wide association study identifies 30 loci associated with bipolar disorder

eQTLGen Consortium; BIOS Consortium; the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41588-019-0397-8

Genome-wide association study identifies 30 loci associated with bipolar disorder

eQTLGen Consortium
, BIOS Consortium
, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

Icahn School of Medicine at Mount Sinai
Broad Institute
Medical Research Council
King's College London
University of Basel
University of Bonn
University of Marburg
University College London
Charité – Universitätsmedizin Berlin
Massachusetts General Hospital
Aarhus University
Karolinska Institutet
University of Würzburg
The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Mental Health Services Capital Region of Denmark
University of Oslo
Vrije Universiteit Amsterdam
deCODE genetics
University of Queensland
Boston Children's Hospital
Cardiff University
University of Michigan, Ann Arbor
IRCCS Istituto di ricerche farmacologiche Mario Negri - Milano, Bergamo, Ranica
The University of Chicago
Berkshire Healthcare NHS Foundation Trust
Rush University Medical Center
Statens Serum Institut
Cornell University
Technische Universität Dresden
Diakonhjemmet Hospital
Utrecht University
University of California at Los Angeles
Ludwig Maximilian University of Munich
University of California at Irvine
University of California at San Francisco
Instituto de Salud Carlos III
Hospital Universitari Vall d'Hebron
Autonomous University of Barcelona
McGill University
Goethe University Frankfurt
University of Edinburgh
University of Iowa
Translational Genomics Research Institute
Max Planck Institute of Psychiatry
Queen Mary University of London
University of Medical Sciences Poznan
University of California at San Diego
University of Antwerp
Johns Hopkins University
University of Bergen
Indiana University-Purdue University Indianapolis
Heidelberg University
Child and Adolescent Psychiatry Research Center
University of Göttingen
Dalhousie University
Queensland Institute of Medical Research
University of Worcester
University of Plymouth
University of New South Wales
Neuroscience Research Australia
University of Minnesota Twin Cities
University Regional Hospital
University of Tübingen
Howard University
Psychiatrie Translationnelle
UMR-S955
University of Toronto
SUNY Downstate Health Sciences University
Barcelona Institute for Global Health
Psychiatry
Psychiatry
VU University Medical Centre Amsterdam
East London NHS Foundation Trust
HudsonAlpha Institute for Biotechnology
University of Illinois at Chicago
National Health Service Scotland
Brigham and Women’s Hospital
Harvard University
International Agency for Research on Cancer
University of Tartu
University of Galway
Trinity College Dublin
Jülich Research Centre
Department of Veterans Affairs
Umeå University
University of Sarajevo
Outpatient Clinic for Bipolar Disorder
Washington University St. Louis
University of Granada
Vanderbilt University
Mayo Clinic Rochester, MN
Stanford University
Scripps Research Translational Institute
University of Iceland
University of Southern California
Mood Disorders
University of Aberdeen
Federal Institute for Drugs and Medical Devices (BfArM)
Psychiatrisches Zentrum
Pfizer
University Health Network
National Institute of Mental Health
University of Melbourne
University of Münster
Assistance publique – Hôpitaux de Paris
Fondation FondaMental
Institut national de la santé et de la recherche médicale
Université Paris Cité
University of Pennsylvania
Alexandru Obregia Clinical Psychiatric Hospital
University of Gothenburg
Johnson & Johnson
Maria Sklodowska-Curie Institute of Oncology
Lindner Center of HOPE
National Institutes of Health
University of Tartu
Norwegian University of Science and Technology
Munich Cluster for Systems Neurology (SyNergy)
University of Liverpool
University of Pittsburgh
University of Copenhagen
Amsterdam UMC
University of Bologna
Hospital Namsos
University of North Carolina at Chapel Hill
University of Barcelona
MHC Sct. Hans
Indiana University Bloomington

Research output: Contribution to journal › Article › peer-review

Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 ⁻⁴ in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 ⁻⁸ ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Original language	English
Pages (from-to)	793-803
Number of pages	11
Journal	Nature Genetics
Volume	51
Issue number	5
DOIs	https://doi.org/10.1038/s41588-019-0397-8
Publication status	Published - 1 May 2019
Externally published	Yes

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10.1038/s41588-019-0397-8

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@article{787c104e2e894fff850828af11df27eb,

title = "Genome-wide association study identifies 30 loci associated with bipolar disorder",

abstract = " Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.",

author = "\{eQTLGen Consortium\} and \{BIOS Consortium\} and \{the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium\} and Stahl, \{Eli A.\} and Gerome Breen and Forstner, \{Andreas J.\} and Andrew McQuillin and Stephan Ripke and Vassily Trubetskoy and Manuel Mattheisen and Yunpeng Wang and Coleman, \{Jonathan R.I.\} and Gaspar, \{H{\'e}l{\'e}na A.\} and \{de Leeuw\}, \{Christiaan A.\} and Stacy Steinberg and Pavlides, \{Jennifer M.Whitehead\} and Maciej Trzaskowski and Byrne, \{Enda M.\} and Pers, \{Tune H.\} and Holmans, \{Peter A.\} and Richards, \{Alexander L.\} and Liam Abbott and Esben Agerbo and Huda Akil and Diego Albani and Ney Alliey-Rodriguez and Als, \{Thomas D.\} and Adebayo Anjorin and Verneri Antilla and Swapnil Awasthi and Badner, \{Judith A.\} and Marie B{\ae}kvad-Hansen and Barchas, \{Jack D.\} and Nicholas Bass and Michael Bauer and Richard Belliveau and Bergen, \{Sarah E.\} and Pedersen, \{Carsten B{\o}cker\} and Erlend B{\o}en and Boks, \{Marco P.\} and James Boocock and Monika Budde and William Bunney and Margit Burmeister and Jonas Bybjerg-Grauholm and William Byerley and Miquel Casas and Felecia Cerrato and Pablo Cervantes and Kimberly Chambert and Charney, \{Alexander W.\} and Danfeng Chen and Sarah Kittel-Schneider",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = may,

day = "1",

doi = "10.1038/s41588-019-0397-8",

language = "English",

volume = "51",

pages = "793--803",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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TY - JOUR

T1 - Genome-wide association study identifies 30 loci associated with bipolar disorder

AU - eQTLGen Consortium

AU - BIOS Consortium

AU - the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

AU - Stahl, Eli A.

AU - Breen, Gerome

AU - Forstner, Andreas J.

AU - McQuillin, Andrew

AU - Ripke, Stephan

AU - Trubetskoy, Vassily

AU - Mattheisen, Manuel

AU - Wang, Yunpeng

AU - Coleman, Jonathan R.I.

AU - Gaspar, Héléna A.

AU - de Leeuw, Christiaan A.

AU - Steinberg, Stacy

AU - Pavlides, Jennifer M.Whitehead

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Pers, Tune H.

AU - Holmans, Peter A.

AU - Richards, Alexander L.

AU - Abbott, Liam

AU - Agerbo, Esben

AU - Akil, Huda

AU - Albani, Diego

AU - Alliey-Rodriguez, Ney

AU - Als, Thomas D.

AU - Anjorin, Adebayo

AU - Antilla, Verneri

AU - Awasthi, Swapnil

AU - Badner, Judith A.

AU - Bækvad-Hansen, Marie

AU - Barchas, Jack D.

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Belliveau, Richard

AU - Bergen, Sarah E.

AU - Pedersen, Carsten Bøcker

AU - Bøen, Erlend

AU - Boks, Marco P.

AU - Boocock, James

AU - Budde, Monika

AU - Bunney, William

AU - Burmeister, Margit

AU - Bybjerg-Grauholm, Jonas

AU - Byerley, William

AU - Casas, Miquel

AU - Cerrato, Felecia

AU - Cervantes, Pablo

AU - Chambert, Kimberly

AU - Charney, Alexander W.

AU - Chen, Danfeng

AU - Kittel-Schneider, Sarah

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

AB - Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

UR - https://www.scopus.com/pages/publications/85065180508

U2 - 10.1038/s41588-019-0397-8

DO - 10.1038/s41588-019-0397-8

M3 - Article

C2 - 31043756

AN - SCOPUS:85065180508

SN - 1061-4036

VL - 51

SP - 793

EP - 803

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association study identifies 30 loci associated with bipolar disorder

Abstract

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