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

Autor:	Hou L; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA., Bergen SE; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA., Akula N; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA., Song J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Hultman CM; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Landén M; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Adli M; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany., Alda M; Department of Psychiatry, Dalhousie University, Halifax, Canada., Ardau R; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy., Arias B; Department of Biologia Animal, Unitat d'Antropologia (Dp. Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain., Aubry JM; Department of Mental Health and Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, Switzerland., Backlund L; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden., Badner JA; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA., Barrett TB; Portland Veterans Affairs Medical Center, Portland, OR, USA., Bauer M; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany., Baune BT; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia., Bellivier F; INSERM UMR-S 1144 - Université Paris Diderot. Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, France., Benabarre A; Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain., Bengesser S; Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria., Berrettini WH; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA., Bhattacharjee AK; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Biernacka JM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA., Birner A; Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria., Bloss CS; Scripps Translational Science Institute, La Jolla, CA, USA., Brichant-Petitjean C; INSERM UMR-S 1144 - Université Paris Diderot. Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, France., Bui ET; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA., Byerley W; Department of Psychiatry, University of California at San Francisco, San Francisco, CA, USA., Cervantes P; McGill University Health Centre, Mood Disorders Program, Montreal, QC, Canada., Chillotti C; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy., Cichon S; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany.; Division of Medical Genetics and Department of Biomedicine, University of Basel, Switzerland., Colom F; Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain., Coryell W; University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Craig DW; The Translational Genomics Research Institute, Phoenix, AZ, USA., Cruceanu C; Douglas Mental Health University Institute, McGill University, Montreal, Canada., Czerski PM; Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland., Davis T; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia., Dayer A; Department of Mental Health and Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, Switzerland., Degenhardt F; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Del Zompo M; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy., DePaulo JR; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Edenberg HJ; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA., Étain B; INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, France., Falkai P; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany., Foroud T; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA., Forstner AJ; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Frisén L; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden., Frye MA; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA., Fullerton JM; Psychiatric Genetics, Neuroscience Research Australia, Sydney, Australia.; School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia., Gard S; Service de Psychiatrie, Hôpital Charles Perrens, Bordeaux, France., Garnham JS; Department of Psychiatry, Dalhousie University, Halifax, Canada., Gershon ES; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA., Goes FS; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Greenwood TA; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Grigoroiu-Serbanescu M; Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania., Hauser J; Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland., Heilbronner U; Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany., Heilmann-Heimbach S; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Herms S; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.; Division of Medical Genetics and Department of Biomedicine, University of Basel, Switzerland., Hipolito M; Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USA., Hitturlingappa S; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia., Hoffmann P; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany.; Division of Medical Genetics and Department of Biomedicine, University of Basel, Switzerland., Hofmann A; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Jamain S; INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, France., Jiménez E; Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain., Kahn JP; Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, France., Kassem L; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA., Kelsoe JR; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Kittel-Schneider S; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany., Kliwicki S; Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland., Koller DL; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA., König B; Department of Psychiatry and Psychotherapeuthic Medicine, Landesklinikum Neunkirchen, Neunkirchen, Austria., Lackner N; Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria., Laje G; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA., Lang M; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Lavebratt C; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden., Lawson WB; Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USA., Leboyer M; INSERM U955, Psychiatrie translationnelle, Université Paris Est Créteil, Pôle de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Créteil, France., Leckband SG; Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USA., Liu C; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA., Maaser A; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Mahon PB; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Maier W; Department of Psychiatry, University of Bonn, Germany., Maj M; Department of Psychiatry, University of Naples SUN, Naples, Italy., Manchia M; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada., Martinsson L; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., McCarthy MJ; Department of Psychiatry, VA San Diego Healthcare System, San Diego, CA, USA., McElroy SL; Lindner Center of HOPE, University of Cincinnati College of Medicine, Mason, OH, USA., McInnis MG; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA., McKinney R; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Mitchell PB; School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, Australia., Mitjans M; Department of Biologia Animal, Unitat d'Antropologia (Dp. Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain., Mondimore FM; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Monteleone P; Department of Psychiatry, University of Naples SUN, Naples, Italy.; Neurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy., Mühleisen TW; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany., Nievergelt CM; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Nöthen MM; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Novák T; National Institute of Mental Health, Klecany, Czech Republic., Nurnberger JI Jr; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Nwulia EA; Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USA., Ösby U; Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden., Pfennig A; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany., Potash JB; Department of Psychiatry, Carver College of Medicine, University of Iowa School of Medicine, Iowa City, IA, USA., Propping P; Institute of Human Genetics, University of Bonn, Germany., Reif A; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany., Reininghaus E; Special Outpatient Center for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria., Rice J; Department of Psychiatry, Washington University School of Medicine in St. Louis., Rietschel M; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Rouleau GA; Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada., Rybakowski JK; Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland., Schalling M; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden., Scheftner WA; Rush University Medical Center, Chicago, IL, USA., Schofield PR; School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.; Mental Illness, Neuroscience Research Australia, Sydney, Australia., Schork NJ; Scripps Translational Science Institute, La Jolla, CA, USA., Schulze TG; Intramural Research Program, National Institute of Mental Health, National Institutes of Health,U.S. Department of Health & Human Services, Bethesda, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Schumacher J; Institute of Human Genetics, University of Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Schweizer BW; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Severino G; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy., Shekhtman T; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Shilling PD; Department of Psychiatry, University of California San Diego, San Diego, CA, USA., Simhandl C; Bipolar Center Wiener Neustadt, Wiener Neustadt, Austria and., Slaney CM; Department of Psychiatry, Dalhousie University, Halifax, Canada., Smith EN; Scripps Translational Science Institute, La Jolla, CA, USA., Squassina A; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy., Stamm T; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany., Stopkova P; National Institute of Mental Health, Klecany, Czech Republic., Streit F; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Strohmaier J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Szelinger S; The Translational Genomics Research Institute, Phoenix, AZ, USA., Tighe SK; Department of Psychiatry, Carver College of Medicine, University of Iowa School of Medicine, Iowa City, IA, USA., Tortorella A; Department of Psychiatry, University of Naples SUN, Naples, Italy., Turecki G; Douglas Mental Health University Institute, McGill University, Montreal, Canada., Vieta E; Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain., Volkert J; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany., Witt SH; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Wright A; School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, Australia., Zandi PP; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Zhang P; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA., Zollner S; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA., McMahon FJ; 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.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2016 Aug 01; Vol. 25 (15), pp. 3383-3394. Date of Electronic Publication: 2016 Jun 21.
DOI:	10.1093/hmg/ddw181
Abstrakt:	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. (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.)
Databáze:	MEDLINE
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