Copy Number Variants in Schizophrenia: Confirmation of Five Previous Findings and New Evidence for 3q29 Microdeletions and VIPR2 Duplications
- Douglas F. Levinson,
M.D. , - Jubao Duan,
Ph.D. , - Sang Oh,
M.Sc. , - Kai Wang,
Ph.D. , - Alan R. Sanders,
M.D. , - Jianxin Shi,
Ph.D. , - Nancy Zhang,
Ph.D. , - Bryan J. Mowry,
M.D., F.R.A.N.Z.C.P. , - Ann Olincy,
M.D. , - Farooq Amin,
M.D. , - C. Robert Cloninger,
M.D. , - Jeremy M. Silverman,
M.D. , - Nancy G. Buccola,
A.P.R.N., B.C. , - William F. Byerley,
M.D. , - Donald W. Black,
M.D. , - Kenneth S. Kendler,
M.D. , - Robert Freedman,
M.D. , - Frank Dudbridge,
Ph.D. , - Itsik Pe'er,
Ph.D. , - Hakon Hakonarson,
M.D., Ph.D. , - Sarah E. Bergen,
Ph.D. , - Ayman H. Fanous,
M.D. , - Peter A. Holmans,
Ph.D. , and - Pablo V. Gejman,
M.D.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the NorthShore University HealthSystem Research Institute, Evanston, Ill.; the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia; the National Cancer Institute, Bethesda, Md.; the Queensland Centre for Mental Health Research and Queensland Institute for Medical Research, Brisbane, Queensland, Australia; the Department of Psychiatry, University of Colorado Denver, Aurora, Colo.; the Department of Psychiatry and Behavioral Sciences, Atlanta VA Medical Center and Emory University, Atlanta; the Department of Psychiatry, Washington University, St. Louis; the Department of Psychiatry, Mount Sinai School of Medicine, New York; the School of Nursing, Louisiana State University Health Sciences Center, New Orleans; the Departments of Psychiatry and Neurology, University of California at San Francisco; the Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Departments of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond; the Department of Statistical Genetics and Epidemiology, London School of Hygiene and Tropical Medicine, London; the Department of Computer Science, Columbia University, New York; the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Mass.; the Department of Psychiatry, Washington VA Medical Center and Georgetown University School of Medicine, Washington, D.C.; and the Biostatistics and Bioinformatics Unit, Cardiff University, Cardiff, U.K.
Abstract
Objective:
To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data.
Method:
After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (<1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and genewise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction.
Results:
In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (>100 kb and >1 Mb) but not duplications.
Conclusions:
The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia.