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Genome scan meta-analysis of schizophrenia and bipolar disorder,part II: Schizophrenia |
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| Authors: | Lewis Cathryn M Levinson Douglas F Wise Lesley H DeLisi Lynn E Straub Richard E Hovatta Iiris Williams Nigel M Schwab Sibylle G Pulver Ann E Faraone Stephen V Brzustowicz Linda M Kaufmann Charles A Garver David L Gurling Hugh M D Lindholm Eva Coon Hilary Moises Hans W Byerley William Shaw Sarah H Mesen Andrea Sherrington Robin O'Neill F Anthony Walsh Dermot Kendler Kenneth S Ekelund Jesper Paunio Tiina Lönnqvist Jouko Peltonen Leena O'Donovan Michael C Owen Michael J Wildenauer Dieter B Maier Wolfgang Nestadt Gerald Blouin Jean-Louis Antonarakis Stylianos E Mowry Bryan J Silverman Jeremy M |
| Affiliation: | 1 Division of Genetics and Development, Guy’s, King’s &; St Thomas’ School of Medicine, London 2 Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, London 3 Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia 4 New York University Medical Center, New York 5 Department of Psychiatry, Columbia University, New York 6 Department of Psychiatry, Mt. Sinai School of Medicine, New York 7 Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda 8 Department of Molecular Medicine, National Public Health Institute, Biomedicum, 9 Department of Mental Health, National Public Health Institute, Helsinki 10 Department of Medical Genetics, University of Helsinki, Biomedicum, Helsinki 11 Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom 12 Department of Psychiatry, University of Bonn, Bonn, Germany 13 Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore 14 Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston 15 Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center, Boston 16 Department of Genetics, Rutgers University, Piscataway, NJ 17 Department of Psychiatry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 18 Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine and Louisville Veterans Affairs Medical Center, Louisville, KY 19 Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden 20 University of Utah, Salt Lake City 21 Molecular Genetics Laboratory, Department of Psychiatry and Psychotherapy, University Hospital Schleswig-Holstein, Kiel, Germany 22 Department of Psychiatry, University of California, Irvine 23 DNA Sciences, Fremont, CA 24 Hospital Nacional Psiquiatrico, Pavas, San Jose, Costa Rica 25 Xenon Genetics, Burnaby, Canada 26 The Department of Psychiatry, The Queens University, Belfast, Northern Ireland 27 The Health Research Board, Dublin, Ireland 28 Department of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond 29 Department of Human Genetics, University of California, Los Angeles 30 Department of Medical Genetics, University of Geneva Medical School, Centre Médical Universitaire, Geneva, Switzerland 31 Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Wacol, Australia 32 Department of Psychiatry, University of Queensland, Brisbane, Australia 33 Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City 34 Department of Psychiatry, Washington University, St. Louis 35 Department of Psychiatry, University of Toronto, Toronto 36 Department of Psychiatry, General Hospital, Iceland 37 Department of Psychiatry, National University Hospital, Reykjavik, Iceland |
| Abstract: | Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations. |
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