Singleton deletions throughout the genome increase risk of bipolar disorder

被引：108

作者：

Zhang, D. ^{[1
]}

Cheng, L. ^{[1
]}

Qian, Y. ^{[1
]}

Alliey-Rodriguez, N. ^{[1
]}

Kelsoe, J. R. ^{[2
]}

Greenwood, T. ^{[2
]}

Nievergelt, C. ^{[2
]}

Barrett, T. B. ^{[2
]}

McKinney, R. ^{[2
]}

Schork, N. ^{[3
,4
]}

Smith, E. N. ^{[3
,4
]}

Bloss, C. ^{[3
,4
]}

Nurnberger, J. ^{[5
]}

Edenberg, H. J. ^{[6
,7
]}

Foroud, T. ^{[7
]}

Sheftner, W. ^{[8
]}

Lawson, W. B. ^{[9
]}

Nwulia, E. A. ^{[9
]}

Hipolito, M. ^{[9
]}

Coryell, W. ^{[10
]}

Rice, J. ^{[11
]}

Byerley, W. ^{[12
]}

McMahon, F. ^{[13
]}

Schulze, T. G. ^{[13
]}

Berrettini, W. ^{[14
]}

Potash, J. B. ^{[15
]}

Belmonte, P. L. ^{[15
]}

Zandi, P. P. ^{[15
]}

McInnis, M. G. ^{[16
]}

Zoellner, S. ^{[16
]}

Craig, D. ^{[17
]}

Szelinger, S. ^{[17
]}

Koller, D. ^{[5
]}

Christian, S. L. ^{[18
]}

Liu, C. ^{[1
]}

Gershon, E. S. ^{[1
,18
]}

机构：

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

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

[3] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA

[4] Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA USA

[5] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA

[6] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA

[7] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[8] Rush Univ, Dept Psychiat, Chicago, IL 60612 USA

[9] Howard Univ, Dept Psychiat, Washington, DC 20059 USA

[10] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA

[11] Washington Univ, Div Biostat, St Louis, MO USA

[12] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA

[13] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD USA

[14] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[15] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA

[16] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA

[17] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA

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

来源：

MOLECULAR PSYCHIATRY | 2009年 / 14卷 / 04期

关键词：

copy number variation; singleton; bipolar disorder; genetics; WIDE ASSOCIATION; COPY NUMBER; SCHIZOPHRENIA; LINKAGE; AUTISM; GENES; LOCI; PCR;

D O I：

10.1038/mp.2008.144

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An overall burden of rare structural genomic variants has not been reported in bipolar disorder ( BD), although there have been reports of cases with microduplication and microdeletion. Here, we present a genome-wide copy number variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single nucleotide polymorphism ( SNP) 6.0 SNP and CNV platform. Singleton deletions ( deletions that appear only once in the dataset) more than 100 kb in length are present in 16.2% of BD cases in contrast to 12.3% of controls ( permutation P = 0.007). This effect was more pronounced for age at onset of mania <= 18 years old. Our results strongly suggest that BD can result from the effects of multiple rare structural variants.

引用

页码：376 / 380

页数：5

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