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Genome scan meta-analysis of schizophrenia and bipolar disorder,part III: Bipolar disorder |
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| Authors: | Segurado Ricardo Detera-Wadleigh Sevilla D Levinson Douglas F Lewis Cathryn M Gill Michael Nurnberger John I Craddock Nick DePaulo J Raymond Baron Miron Gershon Elliot S Ekholm Jenny Cichon Sven Turecki Gustavo Claes Stephan Kelsoe John R Schofield Peter R Badenhop Renee F Morissette J Coon Hilary Blackwood Douglas McInnes L Alison Foroud Tatiana Edenberg Howard J Reich Theodore Rice John P Goate Alison McInnis Melvin G McMahon Francis J Badner Judith A Goldin Lynn R Bennett Phil Willour Virginia L Zandi Peter P Liu Jianjun Gilliam Conrad Juo Suh-Hang Berrettini Wade H Yoshikawa Takeo |
| Institution: | 1 Neuropsychiatric Genetics Unit, Department of Genetics, Trinity College, St. James Hospital, Dublin 2 Trinity Centre for Health Sciences, Department of Psychiatry, St. James Hospital, Dublin 3 Mood and Anxiety Disorders Program, National Institute of Mental Health/National Institutes of Health, National Institutes of Health, Bethesda 4 Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda 5 Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia 6 Division of Genetics and Development, Guy’s, King’s &; St Thomas’ School of Medicine, University College London, London 7 Molecular Psychiatry Laboratory, Windeyer Institute for Medical Science, Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, London 8 Department of Psychiatry, Indiana University, Indianapolis 9 Department of Medical and Molecular Genetics, Indiana University, Indianapolis 10 Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis 11 Molecular Psychiatry Group, Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Edgbaston, Birmingham, United Kingdom 12 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore 13 Division of Psychiatric Genetics, Department of Medical Genetics, Columbia University, New York State Psychiatric Institute, Mount Sinai School of Medicine, New York 14 Departments of Psychiatry and Human Genetics, Mount Sinai School of Medicine, New York 15 Department of Psychiatry, University of Chicago, Chicago 16 Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, National Public Health Institute, Helsinki 17 Department of Mental Health, National Public Health Institute, Helsinki 18 Department of Medical Genetics Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium 19 Department of Psychiatry, University of Antwerp, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium 20 Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium 21 Department of Psychiatry sMcGill University, Montreal 22 Centre for Research in Neuroscience, The Montreal General Hospital Research Institute, McGill University, Montreal 23 Laboratory of Psychiatric Genomics, Department of Psychiatry, University of California San Diego (UCSD), La Jolla 24 Garvan Institute of Medical Research, Macquarie University, Sydney 25 School of Psychiatry, University of New South Wales, and Mood Disorders Unit, Prince of Wales Hospital, Macquarie University, Sydney 26 School of Biological Science, Macquarie University, Sydney 27 Neuroscience Centre Hospitalier de l'Université Laval Research Center and Laval University, Quebec 28 University of Utah, Salt Lake City 29 Psychiatry and Biological Sciences, University of Edinburgh, Edinburgh 30 Department of Psychiatry, Washington University School of Medicine, St. Louis 31 Laboratory for Molecular Psychiatry, RIKEN (Institute of Physical and Chemical Research) Brain Science Institute, Saitama, Japan 32 Departments of Human Genetics University of California, Los Angeles 33 Departments of Psychiatry, University of California, Los Angeles 34 Institute of Human Genetics, University of Bonn, Bonn, Germany 35 Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany 36 Department of Psychiatry, University of Bonn, Bonn, Germany 37 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany 38 Department of Psychiatry, Dalhousie University, Halifax, Canada 39 Department of Psychiatry, University of Ottawa, Ottawa, Canada 40 Department of Psychiatry, Erasme Hospital, University of Brussels, Brussels 41 Department of Clinical Sciences Division of Psychiatry University of Umea, Umea, Sweden 42 Department of Pediatrics, University of California, Irvine 43 Department of Psychiatry, University of California, Irvine 44 Biofrontera Pharmaceuticals, Leverkusen, Germany 45 Department of Psychiatry, University of Texas Health Science Center, San Antonio 46 Department of Psychiatry, University of California, San Francisco 47 Centro de Biología Molecular y Celular San José, Costa Rica 48 Escuela de Medicina, Universidad de Costa Rica, San José, Costa Rica 49 Institute for Basic Psychiatric Research, Aarhus University Hospital, Risskov, Denmark 50 Department of Clinical Biochemistry and Genetics, Odense University Hospital, Odense, Denmark 51 Department of Medical Genetics, University of Geneva Medical School and University Hospitals, Geneva, Switzerland 52 Department of Pediatrics, Hacettepe University, Ankara, Turkey |
| Abstract: | Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for “very narrow” (i.e., BP-I and schizoaffective disorder–BP) and “narrow” (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A “broad” model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region. |
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