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

共 38 条

[21] Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative [J].

Merikangas, Kathleen R. ;

Jin, Robert ;

He, Jian-Ping ;

Kessler, Ronald C. ;

Lee, Sing ;

Sampson, Nancy A. ;

Viana, Maria Carmen ;

Andrade, Laura Helena ;

Hu, Chiyi ;

Karam, Elie G. ;

Ladea, Maria ;

Medina-Mora, Maria Elena ;

Ono, Yutaka ;

Posada-Villa, Jose ;

Sagar, Rajesh ;

Wells, J. Elisabeth ;

Zarkov, Zahari .

ARCHIVES OF GENERAL PSYCHIATRY, 2011, 68 (03) :241-251

[22] Microdeletions of 3q29 Confer High Risk for Schizophrenia [J].

Mulle, Jennifer Gladys ;

Dodd, Anne F. ;

McGrath, John A. ;

Wolyniec, Paula S. ;

Mitchell, Adele A. ;

Shetty, Amol C. ;

Sobreira, Nara L. ;

Valle, David ;

Rudd, M. Katharine ;

Satten, Glen ;

Cutler, David J. ;

Pulver, Ann E. ;

Warren, Stephen T. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2010, 87 (02) :229-236

[23] Functional impact of global rare copy number variation in autism spectrum disorders [J].

Pinto, Dalila ;

Pagnamenta, Alistair T. ;

Klei, Lambertus ;

Anney, Richard ;

Merico, Daniele ;

Regan, Regina ;

Conroy, Judith ;

Magalhaes, Tiago R. ;

Correia, Catarina ;

Abrahams, Brett S. ;

Almeida, Joana ;

Bacchelli, Elena ;

Bader, Gary D. ;

Bailey, Anthony J. ;

Baird, Gillian ;

Battaglia, Agatino ;

Berney, Tom ;

Bolshakova, Nadia ;

Boelte, Sven ;

Bolton, Patrick F. ;

Bourgeron, Thomas ;

Brennan, Sean ;

Brian, Jessica ;

Bryson, Susan E. ;

Carson, Andrew R. ;

Casallo, Guillermo ;

Casey, Jillian ;

Chung, Brian H. Y. ;

Cochrane, Lynne ;

Corsello, Christina ;

Crawford, Emily L. ;

Crossett, Andrew ;

Cytrynbaum, Cheryl ;

Dawson, Geraldine ;

de Jonge, Maretha ;

Delorme, Richard ;

Drmic, Irene ;

Duketis, Eftichia ;

Duque, Frederico ;

Estes, Annette ;

Farrar, Penny ;

Fernandez, Bridget A. ;

Folstein, Susan E. ;

Fombonne, Eric ;

Freitag, Christine M. ;

Gilbert, John ;

Gillberg, Christopher ;

Glessner, Joseph T. ;

Goldberg, Jeremy ;

Green, Andrew .

NATURE, 2010, 466 (7304) :368-372

[24] The bipolar disorder phenome database: A resource for genetic studies [J].

Potash, James B. ;

Toolan, Jennifer ;

Steele, Jo ;

Miller, Erin B. ;

Pearl, Justin ;

Zandi, Peter P. ;

Schulze, Thomas G. ;

Kassem, Layla ;

Simpson, Sylvia G. ;

Lopez, Victor ;

MacKinnon, Dean F. ;

McMahon, Francis J. .

AMERICAN JOURNAL OF PSYCHIATRY, 2007, 164 (08) :1229-1237

[25] Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder [J].

Priebe, L. ;

Degenhardt, F. A. ;

Herms, S. ;

Haenisch, B. ;

Mattheisen, M. ;

Nieratschker, V. ;

Weingarten, M. ;

Witt, S. ;

Breuer, R. ;

Paul, T. ;

Alblas, M. ;

Moebus, S. ;

Lathrop, M. ;

Leboyer, M. ;

Schreiber, S. ;

Grigoroiu-Serbanescu, M. ;

Maier, W. ;

Propping, P. ;

Rietschel, M. ;

Noethen, M. M. ;

Cichon, S. ;

Muehleisen, T. W. .

MOLECULAR PSYCHIATRY, 2012, 17 (04) :421-432

[26] Autistic and Psychiatric Findings Associated With the 3q29 Microdeletion Syndrome: Case Report and Review [J].

Quintero-Rivera, Fabiola ;

Sharifi-Hannauer, Pantea ;

Martinez-Agosto, Julian A. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2010, 152A (10) :2459-2467

[27] Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism [J].

Sanders, Stephan J. ;

Ercan-Sencicek, A. Gulhan ;

Hus, Vanessa ;

Luo, Rui ;

Murtha, Michael T. ;

Moreno-De-Luca, Daniel ;

Chu, Su H. ;

Moreau, Michael P. ;

Gupta, Abha R. ;

Thomson, Susanne A. ;

Mason, Christopher E. ;

Bilguvar, Kaya ;

Celestino-Soper, Patricia B. S. ;

Choi, Murim ;

Crawford, Emily L. ;

Davis, Lea ;

Wright, Nicole R. Davis ;

Dhodapkar, Rahul M. ;

DiCola, Michael ;

DiLullo, Nicholas M. ;

Fernandez, Thomas V. ;

Fielding-Singh, Vikram ;

Fishman, Daniel O. ;

Frahm, Stephanie ;

Garagaloyan, Rouben ;

Goh, Gerald S. ;

Kammela, Sindhuja ;

Klei, Lambertus ;

Lowe, Jennifer K. ;

Lund, Sabata C. ;

McGrew, Anna D. ;

Meyer, Kyle A. ;

Moffat, William J. ;

Murdoch, John D. ;

O'Roak, Brian J. ;

Ober, Gordon T. ;

Pottenger, Rebecca S. ;

Raubeson, Melanie J. ;

Song, Youeun ;

Wang, Qi ;

Yaspan, Brian L. ;

Yu, Timothy W. ;

Yurkiewicz, Liana R. ;

Beaudet, Arthur L. ;

Cantor, Rita M. ;

Curland, Martin ;

Grice, Dorothy E. ;

Guenel, Murat ;

Lifton, Richard P. ;

Mane, Shrikant M. .

NEURON, 2011, 70 (05) :863-885

[28] Strong association of de novo copy number mutations with autism [J].

Sebat, Jonathan ;

Lakshmi, B. ;

Malhotra, Dheeraj ;

Troge, Jennifer ;

Lese-Martin, Christa ;

Walsh, Tom ;

Yamrom, Boris ;

Yoon, Seungtai ;

Krasnitz, Alex ;

Kendall, Jude ;

Leotta, Anthony ;

Pai, Deepa ;

Zhang, Ray ;

Lee, Yoon-Ha ;

Hicks, James ;

Spence, Sarah J. ;

Lee, Annette T. ;

Puura, Kaija ;

Lehtimaeki, Terho ;

Ledbetter, David ;

Gregersen, Peter K. ;

Bregman, Joel ;

Sutcliffe, James S. ;

Jobanputra, Vaidehi ;

Chung, Wendy ;

Warburton, Dorothy ;

King, Mary-Claire ;

Skuse, David ;

Geschwind, Daniel H. ;

Gilliam, T. Conrad ;

Ye, Kenny ;

Wigler, Michael .

SCIENCE, 2007, 316 (5823) :445-449

[29] Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 [J].

Sklar, Pamela ;

Ripke, Stephan ;

Scott, Laura J. ;

Andreassen, Ole A. ;

Cichon, Sven ;

Craddock, Nick ;

Edenberg, Howard J. ;

Nurnberger, John I., Jr. ;

Rietschel, Marcella ;

Blackwood, Douglas ;

Corvin, Aiden ;

Flickinger, Matthew ;

Guan, Weihua ;

Mattingsdal, Morten ;

McQuillin, Andrew ;

Kwan, Phoenix ;

Wienker, Thomas F. ;

Daly, Mark ;

Dudbridge, Frank ;

Holmans, Peter A. ;

Lin, Danyu ;

Burmeister, Margit ;

Greenwood, Tiffany A. ;

Hamshere, Marian L. ;

Muglia, Pierandrea ;

Smith, Erin N. ;

Zandi, Peter P. ;

Nievergelt, Caroline M. ;

McKinney, Rebecca ;

Shilling, Paul D. ;

Schork, Nicholas J. ;

Bloss, Cinnamon S. ;

Foroud, Tatiana ;

Koller, Daniel L. ;

Gershon, Elliot S. ;

Liu, Chunyu ;

Badner, Judith A. ;

Scheftner, William A. ;

Lawson, William B. ;

Nwulia, Evaristus A. ;

Hipolito, Maria ;

Coryell, William ;

Rice, John ;

Byerley, William ;

McMahon, Francis J. ;

Schulze, Thomas G. ;

Berrettini, Wade ;

Lohoff, Falk W. ;

Potash, James B. ;

Mahon, Pamela B. .

NATURE GENETICS, 2011, 43 (10) :977-U162

[30] Genome-wide association study of bipolar disorder in European American and African American individuals [J].

Smith, E. N. ;

Bloss, C. S. ;

Badner, J. A. ;

Barrett, T. ;

Belmonte, P. L. ;

Berrettini, W. ;

Byerley, W. ;

Coryell, W. ;

Craig, D. ;

Edenberg, H. J. ;

Eskin, E. ;

Foroud, T. ;

Gershon, E. ;

Greenwood, T. A. ;

Hipolito, M. ;

Koller, D. L. ;

Lawson, W. B. ;

Liu, C. ;

Lohoff, F. ;

McInnis, M. G. ;

McMahon, F. J. ;

Mirel, D. B. ;

Murray, S. S. ;

Nievergelt, C. ;

Nurnberger, J. ;

Nwulia, E. A. ;

Paschall, J. ;

Potash, J. B. ;

Rice, J. ;

Schulze, T. G. ;

Scheftner, W. ;

Panganiban, C. ;

Zaitlen, N. ;

Zandi, P. P. ;

Zoellner, S. ;

Schork, N. J. ;

Kelsoe, J. R. .

MOLECULAR PSYCHIATRY, 2009, 14 (08) :755-763

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