High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia

被引：228

作者：

Malhotra, Dheeraj ^{[1
,2
,23
]}

McCarthy, Shane ^{[23
]}

Michaelson, Jacob J. ^{[1
,2
]}

Vacic, Vladimir ^{[15
,23
]}

Burdick, Katherine E. ^{[24
]}

Yoon, Seungtai ^{[5
,23
]}

Cichon, Sven ^{[10
,11
,12
]}

Corvin, Aiden ^{[17
,19
]}

Gary, Sydney ^{[23
]}

Gershon, Elliot S. ^{[22
]}

Gill, Michael ^{[17
,19
]}

Karayiorgou, Maria ^{[18
]}

Kelsoe, John R. ^{[2
,4
,21
]}

Krastoshevsky, Olga ^{[20
]}

Krause, Verena ^{[20
]}

Leibenluft, Ellen ^{[7
]}

Levy, Deborah L. ^{[20
]}

Makarov, Vladimir ^{[5
,23
]}

Bhandari, Abhishek ^{[1
,2
,23
]}

Malhotra, Anil K. ^{[6
]}

McMahon, Francis J. ^{[14
]}

Noethen, Markus M. ^{[10
,11
,16
]}

Potash, James B. ^{[8
]}

Rietschel, Marcella ^{[13
]}

Schulze, Thomas G. ^{[9
]}

Sebat, Jonathan ^{[1
,2
,3
,4
,23
]}

机构：

[1] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Dept Cellular Mol & Mol Med, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[5] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY 10029 USA

[6] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY 11004 USA

[7] Emot & Dev Branch, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA

[8] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA

[9] Univ Gottingen, Dept Psychiat & Psychotherapy, D-370075 Gottingen, Germany

[10] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53127 Bonn, Germany

[11] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany

[12] Res Ctr Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany

[13] Univ Heidelberg J5, Cent Inst Mental Hlth, D-68159 Mannheim, Germany

[14] NIMH, NIH, Bethesda, MD 20892 USA

[15] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA

[16] German Ctr Neurodegenerat Dis DZNE, D-53175 Bonn, Germany

[17] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Inst Mol Med, Dublin 2, Ireland

[18] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[19] Trinity Coll Dublin, Dept Psychiat, Dublin 2, Ireland

[20] McLean Hosp, Belmont, MA 02478 USA

[21] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA

[22] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA

[23] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 12824 USA

[24] Mt Sinai Sch Med, New York, NY 10029 USA

来源：

NEURON | 2011年 / 72卷 / 06期

基金：

爱尔兰科学基金会; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; I DISORDER; RISK; MICRODELETIONS; DUPLICATIONS; DELETIONS; SUPPORTS;

D O I：

10.1016/j.neuron.2011.11.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：951 / 963

页数：13

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