High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia

Dheeraj Malhotra; Shane McCarthy; Jacob J Michaelson; Vladimir Vacic; Katherine E Burdick; Seungtai Yoon; Sven Cichon; Aiden Corvin; Sydney Gary; Elliot S Gershon; Michael Gill; Maria Karayiorgou; John R Kelsoe; Olga Krastoshevsky; Verena Krause; Ellen Leibenluft; Deborah L Levy; Vladimir Makarov; Abhishek Bhandari; Anil K Malhotra; Francis J McMahon; Markus M Nöthen; James B Potash; Marcella Rietschel; Thomas G Schulze; Jonathan Sebat

doi:10.1016/j.neuron.2011.11.007

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High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia

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High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia

Dheeraj Malhotra, Shane McCarthy, Jacob J Michaelson, Vladimir Vacic, Katherine E Burdick, Seungtai Yoon, Sven Cichon, Aiden Corvin, Sydney Gary, Elliot S Gershon, …

Neuron (Cambridge, Mass.), Vol.72(6), pp.951-963

2011

DOI: 10.1016/j.neuron.2011.11.007

PMCID: PMC3921625

PMID: 22196331

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Abstract

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases. ► Strong association of rare de novo CNVs with bipolar disorder ► Rare de novo CNVs influence age at disease onset in bipolar disorder ► Replication of earlier findings of a high frequency of de novo CNVs in schizophrenia

Details

Title: Subtitle: High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia
Creators: Dheeraj Malhotra - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA
Shane McCarthy - Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 12824, USA
Jacob J Michaelson - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA
Vladimir Vacic - Department of Computer Science, Columbia University, New York, NY 10027, USA
Katherine E Burdick - Mount Sinai School of Medicine, New York, NY 10029, USA
Seungtai Yoon - Seaver Autism Center, Mount Sinai School of Medicine, New York, NY 10029, USA
Sven Cichon - Department of Genomics, Life and Brain Center, University of Bonn, D-53127 Bonn, Germany
Aiden Corvin - Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland
Sydney Gary - Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 12824, USA
Elliot S Gershon - Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA
Michael Gill - Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland
Maria Karayiorgou - Department of Psychiatry, Columbia University, New York, NY 10032, USA
John R Kelsoe - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA
Olga Krastoshevsky - McLean Hospital, Belmont, MA 02478, USA
Verena Krause - McLean Hospital, Belmont, MA 02478, USA
Ellen Leibenluft - Section on Bipolar Spectrum Disorders, Emotion and Development Branch, NIMH Building 15K - MSC 2670, Bethesda, MD 20892, USA
Deborah L Levy - McLean Hospital, Belmont, MA 02478, USA
Vladimir Makarov - Seaver Autism Center, Mount Sinai School of Medicine, New York, NY 10029, USA
Abhishek Bhandari - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA
Anil K Malhotra - Zucker Hillside hospital, North Shore Long Island Jewish health system, Glen Oaks, NY 11004, USA
Francis J McMahon - Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, NIH, Convent Drive MSC 3719, Bethesda, MD 20892, USA
Markus M Nöthen - Department of Genomics, Life and Brain Center, University of Bonn, D-53127 Bonn, Germany
James B Potash - Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Marcella Rietschel - Central Institute of Mental Health, University of Heidelberg J5, 68159 Mannheim, Germany
Thomas G Schulze - Department of Psychiatry and Psychotherapy, George-August-University Gottingen, von-Siebold-Str.5 370075 Gottingen, Germany
Jonathan Sebat - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.72(6), pp.951-963
Publisher: Elsevier Inc
DOI: 10.1016/j.neuron.2011.11.007
PMID: 22196331
PMCID: PMC3921625
ISSN: 0896-6273
eISSN: 1097-4199
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984070684902771

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