Journal article
Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
Human molecular genetics, Vol.25(15), pp.3383-3394
08/01/2016
DOI: 10.1093/hmg/ddw181
PMCID: PMC5179929
PMID: 27329760
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
Details
- Title: Subtitle
- Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
- Creators
- Liping Hou - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USASarah E Bergen - Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USANirmala Akula - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USAJie Song - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenChristina M Hultman - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenMikael Landén - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenMazda Adli - Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, GermanyMartin Alda - Department of Psychiatry, Dalhousie University, Halifax, CanadaRaffaella Ardau - Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, ItalyBárbara Arias - Department of Biologia Animal, Unitat d'Antropologia (Dp. Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, SpainJean-Michel Aubry - Department of Mental Health and Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, SwitzerlandLena Backlund - Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenJudith A Badner - Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USAThomas B Barrett - Portland Veterans Affairs Medical Center, Portland, OR, USAMichael Bauer - Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, GermanyBernhard T Baune - Discipline of Psychiatry, University of Adelaide, Adelaide, AustraliaFrank Bellivier - INSERM UMR-S 1144 - Université Paris Diderot. Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, FranceAntonio Benabarre - Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, SpainSusanne Bengesser - Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, AustriaWade H Berrettini - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USAAbesh Kumar Bhattacharjee - Department of Psychiatry, University of California San Diego, San Diego, CA, USAJoanna M Biernacka - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USAArmin Birner - Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, AustriaCinnamon S Bloss - Scripps Translational Science Institute, La Jolla, CA, USAClara Brichant-Petitjean - INSERM UMR-S 1144 - Université Paris Diderot. Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, FranceElise T Bui - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USAWilliam Byerley - Department of Psychiatry, University of California at San Francisco, San Francisco, CA, USAPablo Cervantes - McGill University Health Centre, Mood Disorders Program, Montreal, QC, CanadaCaterina Chillotti - Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, ItalySven Cichon - Division of Medical Genetics and Department of Biomedicine, University of Basel, SwitzerlandFrancesc Colom - Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, SpainWilliam Coryell - University of Iowa Hospitals and Clinics, Iowa City, IA, USADavid W Craig - The Translational Genomics Research Institute, Phoenix, AZ, USACristiana Cruceanu - Douglas Mental Health University Institute, McGill University, Montreal, CanadaPiotr M Czerski - Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, PolandTony Davis - Discipline of Psychiatry, University of Adelaide, Adelaide, AustraliaAlexandre Dayer - Department of Mental Health and Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, SwitzerlandFranziska Degenhardt - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyMaria Del Zompo - Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyJ Raymond DePaulo - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USAHoward J Edenberg - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USABruno Étain - INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, FrancePeter Falkai - Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, GermanyTatiana Foroud - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USAAndreas J Forstner - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyLouise Frisén - Child and Adolescent Psychiatry Research Center, Stockholm, SwedenMark A Frye - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USAJanice M Fullerton - School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, AustraliaSébastien Gard - Service de Psychiatrie, Hôpital Charles Perrens, Bordeaux, FranceJulie S Garnham - Department of Psychiatry, Dalhousie University, Halifax, CanadaElliot S Gershon - Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USAFernando S Goes - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USATiffany A Greenwood - Department of Psychiatry, University of California San Diego, San Diego, CA, USAMaria Grigoroiu-Serbanescu - Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, RomaniaJoanna Hauser - Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, PolandUrs Heilbronner - Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, GermanyStefanie Heilmann-Heimbach - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyStefan Herms - Division of Medical Genetics and Department of Biomedicine, University of Basel, SwitzerlandMaria Hipolito - Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USAShashi Hitturlingappa - Discipline of Psychiatry, University of Adelaide, Adelaide, AustraliaPer Hoffmann - Division of Medical Genetics and Department of Biomedicine, University of Basel, SwitzerlandAndrea Hofmann - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyStephane Jamain - INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, FranceEsther Jiménez - Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, SpainJean-Pierre Kahn - Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, FranceLayla Kassem - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USAJohn R Kelsoe - Department of Psychiatry, University of California San Diego, San Diego, CA, USASarah Kittel-Schneider - Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, GermanySebastian Kliwicki - Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, PolandDaniel L Koller - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USABarbara König - Department of Psychiatry and Psychotherapeuthic Medicine, Landesklinikum Neunkirchen, Neunkirchen, AustriaNina Lackner - Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, AustriaGonzalo Laje - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USAMaren Lang - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyCatharina Lavebratt - Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenWilliam B Lawson - Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USAMarion Leboyer - INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, FranceSusan G Leckband - Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USAChunyu Liu - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USAAnna Maaser - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyPamela B Mahon - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USAWolfgang Maier - Department of Psychiatry, University of Bonn, GermanyMario Maj - Department of Psychiatry, University of Naples SUN, Naples, ItalyMirko Manchia - Department of Pharmacology, Dalhousie University, Halifax, NS, CanadaLina Martinsson - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenMichael J McCarthy - Department of Psychiatry, VA San Diego Healthcare System, San Diego, CA, USASusan L McElroy - Lindner Center of HOPE, University of Cincinnati College of Medicine, Mason, OH, USAMelvin G McInnis - Department of Psychiatry, University of Michigan, Ann Arbor, MI, USARebecca McKinney - Department of Psychiatry, University of California San Diego, San Diego, CA, USAPhilip B Mitchell - School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, AustraliaMarina Mitjans - Department of Biologia Animal, Unitat d'Antropologia (Dp. Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, SpainFrancis M Mondimore - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USAPalmiero Monteleone - Neurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, ItalyThomas W Mühleisen - Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, GermanyCaroline M Nievergelt - Department of Psychiatry, University of California San Diego, San Diego, CA, USAMarkus M Nöthen - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyTomas Novák - National Institute of Mental Health, Klecany, Czech RepublicJohn I Nurnberger Jr - Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USAEvaristus A Nwulia - Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USAUrban Ösby - Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenAndrea Pfennig - Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, GermanyJames B Potash - Department of Psychiatry, Carver College of Medicine, University of Iowa School of Medicine, Iowa City, IA, USAPeter Propping - Institute of Human Genetics, University of Bonn, GermanyAndreas Reif - Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, GermanyEva Reininghaus - Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, AustriaJohn Rice - Department of Psychiatry, Washington University School of Medicine in St. LouisMarcella Rietschel - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyGuy A Rouleau - Montreal Neurological Institute and Hospital, McGill University, Montreal, CanadaJanusz K Rybakowski - Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, PolandMartin Schalling - Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenWilliam A Scheftner - Rush University Medical Center, Chicago, IL, USAPeter R Schofield - Mental Illness, Neuroscience Research Australia, Sydney, AustraliaNicholas J Schork - Scripps Translational Science Institute, La Jolla, CA, USAThomas G Schulze - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyJohannes Schumacher - Department of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyBarbara W Schweizer - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USAGiovanni Severino - Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyTatyana Shekhtman - Department of Psychiatry, University of California San Diego, San Diego, CA, USAPaul D Shilling - Department of Psychiatry, University of California San Diego, San Diego, CA, USAChristian Simhandl - Bipolar Center Wiener Neustadt, Wiener Neustadt, Austria andClaire M Slaney - Department of Psychiatry, Dalhousie University, Halifax, CanadaErin N Smith - Scripps Translational Science Institute, La Jolla, CA, USAAlessio Squassina - Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyThomas Stamm - Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, GermanyPavla Stopkova - National Institute of Mental Health, Klecany, Czech RepublicFabian Streit - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyJana Strohmaier - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanySzabolcs Szelinger - The Translational Genomics Research Institute, Phoenix, AZ, USASarah K Tighe - Department of Psychiatry, Carver College of Medicine, University of Iowa School of Medicine, Iowa City, IA, USAAlfonso Tortorella - Department of Psychiatry, University of Naples SUN, Naples, ItalyGustavo Turecki - Douglas Mental Health University Institute, McGill University, Montreal, CanadaEduard Vieta - Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, SpainJulia Volkert - Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, GermanyStephanie H Witt - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyAdam Wright - School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, AustraliaPeter P Zandi - Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAPeng Zhang - Department of Psychiatry, University of Michigan, Ann Arbor, MI, USASebastian Zollner - Department of Psychiatry, University of Michigan, Ann Arbor, MI, USAFrancis J McMahon - Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA, mcmahonf@mail.nih.gov
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.25(15), pp.3383-3394
- Publisher
- England
- DOI
- 10.1093/hmg/ddw181
- PMID
- 27329760
- PMCID
- PMC5179929
- ISSN
- 1460-2083
- eISSN
- 1460-2083
- Grant note
- R01 MH101822 / NIMH NIH HHS K02 DA021237 / NIDA NIH HHS R01 MH059535 / NIMH NIH HHS Wellcome Trust R01 MH101810 / NIMH NIH HHS R01 MH090936 / NIMH NIH HHS R01 MH101819 / NIMH NIH HHS R01 MH101814 / NIMH NIH HHS R01 MH090948 / NIMH NIH HHS R01 MH059548 / NIMH NIH HHS UL1 TR001108 / NCATS NIH HHS R01 MH101825 / NIMH NIH HHS R01 MH090941 / NIMH NIH HHS R01 MH059567 / NIMH NIH HHS R01 MH059556 / NIMH NIH HHS R01 DA006227 / NIDA NIH HHS Z01 MH002810 / Intramural NIH HHS HHSN261200800001C / CCR NIH HHS R01 MH059545 / NIMH NIH HHS R01 DA033684 / NIDA NIH HHS R01 MH059533 / NIMH NIH HHS R01 MH101820 / NIMH NIH HHS R01 MH101782 / NIMH NIH HHS R01 MH059534 / NIMH NIH HHS HHSN268201000029C / NHLBI NIH HHS R01 MH059553 / NIMH NIH HHS R01 MH090951 / NIMH NIH HHS R01 MH090937 / NIMH NIH HHS P01 CA089392 / NCI NIH HHS R01 MH060068 / NIMH NIH HHS HHSN261200800001E / NCI NIH HHS
- Language
- English
- Date published
- 08/01/2016
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003453802771
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