TY - JOUR
T1 - Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q
T2 - Schizophrenia linkage collaborative group III
AU - Levinson, Douglas F.
AU - Holmans, Peter
AU - Straub, Richard E.
AU - Owen, Michael J.
AU - Wildenauer, Dieter B.
AU - Gejman, Pablo V.
AU - Pulver, Ann E.
AU - Laurent, Claudine
AU - Kendler, Kenneth S.
AU - Walsh, Dermot
AU - Norton, N.
AU - Williams, Nigel M.
AU - Schwab, Sibylle G.
AU - Lerer, Bernard
AU - Mowry, Bryan J.
AU - Sanders, Alan R.
AU - Antonarakis, Stylianos E.
AU - Blouin, Jean Louis
AU - DeLeuze, Jean Francois
AU - Mallet, Jacques
N1 - Funding Information:
The assistance of the following collaborators is gratefully acknowledged: MCV/Ireland: F. Anthony O'Neill (The Queen's University, Belfast). U Wales: Michael O'Donovan, Alastair Cardno, Kieran Murphy, Lisa Jones, and Robert Sanders (University of Wales College of Medicine, Cardiff); Peter McGuffin (Institute of Psychiatry, London). U Bonn: Wolfgang Maier (University of Bonn); Margot Albus, (State Mental Hospital, Haar, Germany). US/Aust: Simon J. Foote and Kelly R. Ewen (Australian Genome Research Facility, Melbourne); Deborah Nertney, David Lennon, and Helen Jones (Wolston Park Hospital, Brisbane); Derek Nancarrow and Nicholas Hayward (Queensland Institute of Medical Research, Brisbane); Matthew O'Brien and Catherine Thornley (Mental Health Research Institute, Melbourne); Madeline Gladis (University of Pennsylvania); Jeremy Silverman, Richard Mohs, Larry Siever, Christopher Smith (Mt. Sinai Medical School, New York); Raymond Crowe, Donald Black and Nancy Andreasen (University of Iowa); Jean Endicott and Larry Sharpe (Columbia University, New York). U Chicago: Qiuhe Cao, Jing Zhang, Juliet J. Guroff, Mary E. Maxwell, Diane Kazuba, and Elliot S. Gershon (University of Chicago). JHU: Gerald Nestadt and staff of the JHU Epidemiology-Genetics Program in Psychiatry; Corinne Gehrig, Uppala Radhakrishna, and Genevieve Duriaux Saïl (University of Geneva). CNRS: Stephane Soubigou, Dominique Campion, Maurice Jay, Florence Thibaut, Michel de Chaldee, and Fabienne Treilhou (CNRS). Specimens from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH SGI) were utilized in this study, with genotyping by the US/Australia group (Australian Genome Research Facility, Drs. Foote and Ewen). Data and biomaterials were collected in three projects that participated in the NIMH-SGI. From 1991–1997, the Principal Investigators and Co-Investigators were: Harvard University, Boston, MA, U01 MH46318, Ming T. Tsuang, M.D., Ph.D., D.Sc., Stephen Faraone, Ph.D., and John Pepple, Ph.D.; Washington University, St. Louis, MO, U01 MH46276, C. Robert Cloninger, M.D., Theodore Reich, M.D., and Dragan Svrakic, M.D.; Columbia University, New York, NY U01 MH46289, Charles Kaufmann, M.D., Dolores Malaspina, M.D., and Jill Harkavy Friedman, Ph.D. Financial support for this project was provided by NIMH grants MH 41953, 52537, and 45390 (MCV/Ireland); Medical Research Council (United Kingdom) (U Wales); Deutsche Forschungsgemeinschaft (Bonn); NIMH grants MH45097 and KO201207 and the Beukenkamp Foundation (Philadelphia); National Health and Medical Research Council of Australia (NHMRC) grants 33505, 35016, Rebecca L. Cooper Medical Research Foundation, Queensland Department of Health, and NHMRC Network for Brain Research into Mental Disorders (B.J.M.); the National Institute of Mental Health Intramural Program (U Chicago); Novartis, and University Hospitals of Geneva (JHU); l'Association Francaise contre les Myopathies, and Aventis SA (CNRS). We are grateful to all of the family members and clinicians whose contributions have made this study possible.
PY - 2000
Y1 - 2000
N2 - Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1, 003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n = 1, 937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value < .0002 with, or P = .0004 without, inclusion of the sample that produced the first positive report in this region; the maximum NPL score in this region was 2.47 (P = .0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P = .0036), and there was significant evidence for intersample heterogeneity (empirical P = .0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P = .045 and with significant evidence for intersample heterogeneity (empirical P = .0096).
AB - Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1, 003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n = 1, 937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value < .0002 with, or P = .0004 without, inclusion of the sample that produced the first positive report in this region; the maximum NPL score in this region was 2.47 (P = .0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P = .0036), and there was significant evidence for intersample heterogeneity (empirical P = .0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P = .045 and with significant evidence for intersample heterogeneity (empirical P = .0096).
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U2 - 10.1086/303041
DO - 10.1086/303041
M3 - Article
C2 - 10924404
AN - SCOPUS:0033842462
SN - 0002-9297
VL - 67
SP - 652
EP - 663
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -