Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Cathryn M Lewis; Douglas F Levinson; Lesley H Wise; Lynn E DeLisi; Richard E Straub; Iiris Hovatta; Nigel M Williams; Sibylle G Schwab; Ann E Pulver; Stephen V Faraone; Linda M Brzustowicz; Charles A Kaufmann; David L Garver; Hugh M.D Gurling; Eva Lindholm; Hilary Coon; Hans W Moises; William Byerley; Sarah H Shaw; Andrea Mesen; Robin Sherrington; F. Anthony O’Neill; Dermot Walsh; Kenneth S Kendler; Jesper Ekelund; Tiina Paunio; Jouko Lönnqvist; Leena Peltonen; Michael C O’Donovan; Michael J Owen; Dieter B Wildenauer; Wolfgang Maier; Gerald Nestadt; Jean-Louis Blouin; Stylianos E Antonarakis; Bryan J Mowry; Jeremy M Silverman; Raymond R Crowe; C. Robert Cloninger; Ming T Tsuang; Dolores Malaspina; Jill M Harkavy-Friedman; Dragan M Svrakic; Anne S Bassett; Jennifer Holcomb; Gursharan Kalsi; Andrew McQuillin; Jon Brynjolfson; Thordur Sigmundsson; Hannes Petursson; Elena Jazin; Tomas Zoëga; Tomas Helgason

doi:10.1086/376549

Back

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Journal article

Open access

Peer reviewed

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Cathryn M Lewis, Douglas F Levinson, Lesley H Wise, Lynn E DeLisi, Richard E Straub, Iiris Hovatta, Nigel M Williams, Sibylle G Schwab, Ann E Pulver, Stephen V Faraone, …

American journal of human genetics, Vol.73(1), pp.34-48

2003

DOI: https://doi.org/10.1086/376549

PMCID: PMC1180588

PMID: 12802786

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 [ affected cases ] ). 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 ( P AvgRnk<.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.

Files and links (1)

url

https://doi.org/10.1086/376549View

Version of Record (VoR) Open

Metrics

11 Record Views

924 Times Cited - Web of Science

See more details

Details

Title: Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia
Creators: Cathryn M Lewis - Division of Genetics and Development, Guy’s, King’s & St Thomas’ School of Medicine, London
Douglas F Levinson - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia
Lesley H Wise - Division of Genetics and Development, Guy’s, King’s & St Thomas’ School of Medicine, London
Lynn E DeLisi - New York University Medical Center, New York
Richard E Straub - Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda
Iiris Hovatta - Department of Molecular Medicine, National Public Health Institute, Biomedicum
Nigel M Williams - Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom
Sibylle G Schwab - Department of Psychiatry, University of Bonn, Bonn, Germany
Ann E Pulver - Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore
Stephen V Faraone - Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
Linda M Brzustowicz - Department of Genetics, Rutgers University, Piscataway, NJ
Charles A Kaufmann - Department of Psychiatry, Columbia University, New York
David L Garver - Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine and Louisville Veterans Affairs Medical Center, Louisville, KY
Hugh M.D Gurling - Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, London
Eva Lindholm - Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
Hilary Coon - University of Utah, Salt Lake City
Hans W Moises - Molecular Genetics Laboratory, Department of Psychiatry and Psychotherapy, University Hospital Schleswig-Holstein, Kiel, Germany
William Byerley - Department of Psychiatry, University of California, Irvine
Sarah H Shaw - DNA Sciences, Fremont, CA
Andrea Mesen - Hospital Nacional Psiquiatrico, Pavas, San Jose, Costa Rica
Robin Sherrington - Xenon Genetics, Burnaby, Canada
F. Anthony O’Neill - The Department of Psychiatry, The Queens University, Belfast, Northern Ireland
Dermot Walsh - The Health Research Board, Dublin, Ireland
Kenneth S Kendler - Department of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond
Jesper Ekelund - Department of Molecular Medicine, National Public Health Institute, Biomedicum
Tiina Paunio - Department of Molecular Medicine, National Public Health Institute, Biomedicum
Jouko Lönnqvist - Department of Mental Health, National Public Health Institute, Helsinki
Leena Peltonen - Department of Molecular Medicine, National Public Health Institute, Biomedicum
Michael C O’Donovan - Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom
Michael J Owen - Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom
Dieter B Wildenauer - Department of Psychiatry, University of Bonn, Bonn, Germany
Wolfgang Maier - Department of Psychiatry, University of Bonn, Bonn, Germany
Gerald Nestadt - Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore
Jean-Louis Blouin - Department of Medical Genetics, University of Geneva Medical School, Centre Médical Universitaire, Geneva, Switzerland
Stylianos E Antonarakis - Department of Medical Genetics, University of Geneva Medical School, Centre Médical Universitaire, Geneva, Switzerland
Bryan J Mowry - Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Wacol, Australia
Jeremy M Silverman - Department of Psychiatry, Mt. Sinai School of Medicine, New York
Raymond R Crowe - Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City
C. Robert Cloninger - Department of Psychiatry, Washington University, St. Louis
Ming T Tsuang - Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center, Boston
Dolores Malaspina - Department of Psychiatry, Columbia University, New York
Jill M Harkavy-Friedman - Department of Psychiatry, Columbia University, New York
Dragan M Svrakic - Department of Psychiatry, Washington University, St. Louis
Anne S Bassett - Department of Psychiatry, University of Toronto, Toronto
Jennifer Holcomb - Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine and Louisville Veterans Affairs Medical Center, Louisville, KY
Gursharan Kalsi - Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, London
Andrew McQuillin - Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, London
Jon Brynjolfson - Department of Psychiatry, General Hospital, Iceland
Thordur Sigmundsson - Department of Psychiatry, General Hospital, Iceland
Hannes Petursson - Department of Psychiatry, General Hospital, Iceland
Elena Jazin - Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
Tomas Zoëga - Department of Psychiatry, National University Hospital, Reykjavik, Iceland
Tomas Helgason - Department of Psychiatry, National University Hospital, Reykjavik, Iceland
Publication Details: American journal of human genetics, Vol.73(1), pp.34-48
Date published: 2003
Publisher: Elsevier Inc
Academic Unit: Genetics (SAS); Human Genetics Institute of New Jersey
Language: English
Resource Type: Journal article
Identifiers: 991031665676704646