Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept

被引：156

作者：

Franke, Barbara ^{[1
,2
,3
]}

Stein, Jason L. ^{[4
,5
]}

Ripke, Stephan ^{[6
,7
,8
]}

Anttila, Verneri ^{[6
,7
]}

Hibar, Derrek P. ^{[4
]}

van Hulzen, Kimm J. E. ^{[1
,3
]}

Arias-Vasquez, Alejandro ^{[1
,2
,3
,9
]}

Smoller, Jordan W. ^{[7
,10
,11
]}

Nichols, Thomas E. ^{[12
,13
,14
]}

Neale, Michael C. ^{[15
,16
]}

McIntosh, Andrew M. ^{[17
]}

Lee, Phil ^{[7
,10
,11
]}

McMahon, Francis J. ^{[18
]}

Meyer-Lindenberg, Andreas ^{[19
]}

Mattheisen, Manuel ^{[20
,21
,22
,23
]}

Andreassen, Ole A. ^{[24
,25
]}

Gruber, Oliver ^{[26
]}

Sachdev, Perminder S. ^{[27
,28
]}

Roiz-Santianez, Roberto ^{[29
,30
]}

Saykin, Andrew J. ^{[31
,32
,33
]}

Ehrlich, Stefan ^{[34
,35
]}

Mather, Karen A. ^{[27
]}

Turner, Jessica A. ^{[36
,37
]}

Wright, Margaret J. ^{[38
,39
]}

O'Donovan, Michael C. ^{[40
,41
]}

Thompson, Paul M. ^{[4
]}

Neale, Benjamin M. ^{[6
,7
,10
,42
]}

Medland, Sarah E. ^{[38
]}

Sullivan, Patrick F. ^{[43
,44
,45
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands

[4] Univ So Calif, Keck Sch Med, Imaging Genet Ctr, Mark & Mary Stevens Neuroimaging & Informat Inst, Marina Del Rey, CA USA

[5] Univ Calif Los Angeles, Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90024 USA

[6] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

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

[8] Charite, Dept Psychiat & Psychotherapy, Campus Charite Mitte, D-13353 Berlin, Germany

[9] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands

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

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

[12] Univ Oxford, FMRIB Ctr, Oxford, England

[13] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England

[14] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England

[15] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA

[16] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA

[17] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[18] NIH, US Dept HHS, Intramural Res Program, Bethesda, MD USA

[19] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany

[20] Aarhus Univ, Dept Biomed, iPSYCH, Aarhus, Denmark

[21] IPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark

[22] IPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark

[23] Aarhus Univ, ISEQ, Ctr Integrated Sequencing, iPSYCH, Aarhus, Denmark

[24] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway

[25] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[26] Univ Med Ctr, Dept Psychiat & Psychotherapy, Ctr Translat Res Syst Neurosci & Psychia, Gottingen, Germany

[27] Univ New S Wales, Sch Psychiat, Ctr Healthy Brain Ageing, Sydney, NSW, Australia

[28] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia

[29] Univ Cantabria IDIVAL, Sch Med, Univ Hosp Marques Valdecilla, Dept Psychiat, Santander, Spain

[30] Cibersam Ctr Invest Biomed Red Salud Mental, Madrid, Spain

[31] Indiana Univ Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN 46202 USA

[32] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA

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

[34] Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, D-01062 Dresden, Germany

[35] Tech Univ Dresden, Univ Hosp, D-01062 Dresden, Germany

[36] Georgia State Univ, Atlanta, GA 30303 USA

[37] Mind Res Network, Albuquerque, NM USA

[38] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[39] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia

[40] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Gen, Cardiff CF10 3AX, S Glam, Wales

[41] Cardiff Univ, Natl Ctr Mental Hlth, Cardiff CF10 3AX, S Glam, Wales

[42] Broad Inst MIT & Harvard Cambridge, Med & Populat Genet Program, Cambridge, MA USA

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

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

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

来源：

NATURE NEUROSCIENCE | 2016年 / 19卷 / 03期

基金：

澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 澳大利亚研究理事会; 英国医学研究理事会; 瑞典研究理事会; 英国惠康基金; 芬兰科学院; 加拿大健康研究院; 美国国家科学基金会; 欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; METAANALYSIS; ENDOPHENOTYPE; INDIVIDUALS; PERSPECTIVE; PHENOTYPES; DISORDERS; DISCOVERY; RELATIVES; VARIANTS;

D O I：

10.1038/nn.4228

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

引用

页码：420 / +

页数：14

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