Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases

被引：39

作者：

Charney, Alexander W. ^{[1
,2
,3
,4
]}

Stahl, Eli A. ^{[4
]}

Green, Elaine K. ^{[32
,33
]}

Chen, Chia-Yen ^{[13
,14
]}

Moran, Jennifer L. ^{[15
]}

Chambert, Kimberly ^{[13
]}

Belliveau, Richard A., Jr. ^{[13
]}

Forty, Liz ^{[34
]}

Gordon-Smith, Katherine ^{[35
]}

Lee, Phil H. ^{[13
,16
,18
]}

Bromet, Evelyn J. ^{[6
]}

Buckley, Peter F. ^{[21
,22
]}

Escamilla, Michael A. ^{[24
]}

Fanous, Ayman H. ^{[7
,9
]}

Fochtmann, Laura J. ^{[6
]}

Lehrer, Douglas S. ^{[27
]}

Malaspina, Dolores ^{[1
,3
,4
,5
]}

Marder, Stephen R. ^{[25
]}

Morley, Christopher P. ^{[10
,11
,12
]}

Nicolini, Humberto ^{[36
,37
]}

Perkins, Diana O. ^{[28
]}

Rakofsky, Jeffrey J. ^{[23
]}

Rapaport, Mark H. ^{[23
]}

Medeiros, Helena ^{[7
]}

Sobell, Janet L. ^{[26
]}

Backlund, Lena ^{[38
]}

Bergen, Sarah E. ^{[39
]}

Jureus, Anders ^{[39
]}

Schalling, Martin ^{[40
]}

Lichtenstein, Paul ^{[39
]}

Knowles, James A. ^{[8
]}

Burdick, Katherine E. ^{[1
,18
,20
]}

Jones, Ian ^{[34
]}

Jones, Lisa A. ^{[35
]}

Hultman, Christina M. ^{[1
,39
]}

Perlis, Roy ^{[17
]}

Purcell, Shaun M. ^{[18
,20
]}

McCarroll, Steven A. ^{[13
,19
]}

Pato, Carlos N. ^{[7
]}

Pato, Michele T. ^{[7
]}

Di Florio, Ariana ^{[28
,34
]}

Craddock, Nick ^{[34
]}

Landen, Mikael ^{[39
,41
]}

Smoller, Jordan W. ^{[13
,14
]}

Ruderfer, Douglas M. ^{[29
,30
,31
]}

Sklar, Pamela ^{[1
,3
,4
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Psychiat, Friedman Brain Inst, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Neurosurg, Friedman Brain Inst, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Neurosci, Friedman Brain Inst, New York, NY 10029 USA

[4] Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA

[5] NYU, Dept Psychiat, 550 1St Ave, New York, NY 10016 USA

[6] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA

[7] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA

[8] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA

[9] VA New York Harbor Healthcare Syst, Dept Psychiat, Brooklyn, NY USA

[10] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA

[11] SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY 13210 USA

[12] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA

[13] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA

[14] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[15] Massachusetts Gen Hosp, Ctr Genom Med, Dept Psychiat, Boston, MA 02114 USA

[16] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[17] Massachusetts Gen Hosp, Ctr Expt Therapeut, Boston, MA 02114 USA

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

[19] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[20] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA

[21] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA

[22] Georgia Regents Univ, Dept Psychiat, Med Ctr, Augusta, GA USA

[23] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[24] Texas Tech Univ, Hlth Sci Ctr El Paso, Ctr Excellence Neurosci, Dept Psychiat, El Paso, TX USA

[25] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA

[26] Univ Southern Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA

[27] Wright State Univ, Dept Psychiat, Dayton, OH 45435 USA

[28] Univ North Carolina Chapel Hill, Dept Psychiat, Chapel Hill, NC USA

[29] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Dept Med,Div Genet Med, Nashville, TN 37232 USA

[30] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Dept Biomed Informat, Nashville, TN 37232 USA

[31] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Dept Psychiat, Nashville, TN 37232 USA

[32] Plymouth Univ, Peninsula Sch Med, Sch Biomed & Hlth Sci, Portland Sq, Plymouth, Devon, England

[33] Plymouth Univ, Peninsula Sch Dent, Portland Sq, Plymouth, Devon, England

[34] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales

[35] Univ Birmingham, Dept Psychiat, Birmingham, W Midlands, England

[36] Univ Autonoma Ciudad Mexico, Ctr Genom Sci, Mexico City, DF, Mexico

[37] Carracci Med Grp, Dept Psychiat, Mexico City, DF, Mexico

[38] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[39] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[40] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[41] Gothenburg Univ, Sahlgenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden

来源：

BIOLOGICAL PSYCHIATRY | 2019年 / 86卷 / 02期

基金：

瑞典研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

Bipolar disorder; Copy number variant; Genetics; Polygenic risk score; Rare variant burden; Schizophrenia; GENOME-WIDE ASSOCIATION; DE-NOVO CNVS; INCREASE RISK; DELETIONS; DUPLICATIONS;

D O I：

10.1016/j.biopsych.2018.12.009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

BACKGROUND: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood. METHODS: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis. RESULTS: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p =.001), BD I (p =.0003), and BD II (p =.0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p =.0007, PRS p =.004), and BD I without psychosis (CNV p =.0004, PRS p = 3.9 X 10(25)). Within BD I, psychosis was associated with increased schizophrenia PRSs (p =.005) but not CNV burden. CONCLUSIONS: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

引用

页码：110 / 119

页数：10

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