Microduplications of 16p11.2 are associated with schizophrenia

被引：518

作者：

McCarthy, Shane E. ^{[1
]}

Makarov, Vladimir ^{[1
]}

Kirov, George ^{[2
]}

Addington, Anjene M. ^{[3
]}

McClellan, Jon ^{[4
]}

Yoon, Seungtai ^{[1
]}

Perkins, Diana O. ^{[5
]}

Dickel, Diane E. ^{[6
]}

Kusenda, Mary ^{[1
,7
]}

Krastoshevsky, Olga ^{[8
]}

Krause, Verena ^{[8
]}

Kumar, Ravinesh A. ^{[9
]}

Grozeva, Detelina ^{[2
]}

Malhotra, Dheeraj ^{[1
]}

Walsh, Tom ^{[6
]}

Zackai, Elaine H. ^{[10
]}

Kaplan, Paige ^{[11
]}

Ganesh, Jaya ^{[11
]}

Krantz, Ian D. ^{[10
]}

Spinner, Nancy B. ^{[10
]}

Roccanova, Patricia ^{[1
]}

Bhandari, Abhishek ^{[1
]}

Pavon, Kevin ^{[1
]}

Lakshmi, B. ^{[1
,12
]}

Leotta, Anthony ^{[1
]}

Kendall, Jude ^{[1
]}

Lee, Yoon-ha ^{[1
]}

Vacic, Vladimir ^{[1
]}

Gary, Sydney ^{[1
]}

Iakoucheva, Lilia M. ^{[13
]}

Crow, Timothy J. ^{[14
]}

Christian, Susan L. ^{[9
]}

Lieberman, Jeffrey A. ^{[15
,16
]}

Stroup, T. Scott ^{[15
]}

Lehtimaki, Terho ^{[17
]}

Puura, Kaija ^{[18
,19
]}

Haldeman-Englert, Chad ^{[10
]}

Pearl, Justin ^{[20
]}

Goodell, Meredith ^{[21
]}

Willour, Virginia L. ^{[21
]}

DeRosse, Pamela ^{[22
]}

Steele, Jo ^{[20
]}

Kassem, Layla ^{[20
]}

Wolff, Jessica ^{[20
]}

Chitkara, Nisha ^{[22
]}

McMahon, Francis J. ^{[20
]}

Malhotra, Anil K. ^{[22
]}

Potash, James B. ^{[21
]}

Schulze, Thomas G. ^{[20
,23
]}

Noethen, Markus M. ^{[24
,25
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[2] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales

[3] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA

[4] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA

[5] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA

[6] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[7] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA

[8] McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA

[9] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[10] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[11] Childrens Hosp Philadelphia, Sect Biochem Genet, Philadelphia, PA 19104 USA

[12] Ontario Inst Canc Res, Toronto, ON, Canada

[13] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA

[14] Warneford Hosp, Prince Wales Int Ctr SANE Res, Oxford OX3 7JX, England

[15] Columbia Univ, Columbia Univ Coll Phys & Surg, New York, NY USA

[16] New York State Psychiat Hosp, New York, NY USA

[17] Tampere Univ, Dept Clin Chem, FIN-33101 Tampere, Finland

[18] Tampere Univ, Dept Child Psychiat, FIN-33101 Tampere, Finland

[19] Univ Hosp, Tampere, Finland

[20] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bethesda, MD 20892 USA

[21] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA

[22] Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA

[23] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany

[24] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany

[25] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany

[26] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany

[27] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA

[28] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA USA

[29] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN USA

[30] UCL, Behav Sci Unit, Inst Child Hlth, London, England

[31] Trinity Coll Dublin, Sch Med, Dept Psychiat, Dublin, Ireland

[32] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA

[33] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA

[34] VA Boston Healthcare Syst, Brockton, MA USA

[35] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[36] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Waltham, MA USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

关键词：

PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDER; HEAD CIRCUMFERENCE; RECURRENT REARRANGEMENTS; HUMAN GENOME; 1ST YEAR; INDIVIDUALS; DISRUPTION; DELETIONS; GENES;

D O I：

10.1038/ng.474

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders(1-3). We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

引用

页码：1223 / U85

页数：7

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