Genome-wide association study identifies five new schizophrenia loci

被引：1458

作者：

Ripke, Stephan ^{[2
]}

Sanders, Alan R. ^{[1
,3
]}

Kendler, Kenneth S. ^{[4
,5
,6
]}

Levinson, Douglas F. ^{[7
]}

Sklar, Pamela ^{[2
,8
]}

Holmans, Peter A. ^{[9
,10
]}

Lin, Dan-Yu ^{[11
]}

Duan, Jubao ^{[1
,3
]}

Ophoff, Roel A. ^{[12
,13
,14
,15
]}

Andreassen, Ole A. ^{[16
,17
]}

Scolnick, Edward ^{[18
]}

Cichon, Sven ^{[19
,20
,21
]}

Clair, David St. ^{[22
]}

Corvin, Aiden ^{[23
]}

Gurling, Hugh ^{[24
]}

Werge, Thomas ^{[25
]}

Rujescu, Dan ^{[26
]}

Blackwood, Douglas H. R. ^{[27
]}

Pato, Carlos N. ^{[28
]}

Malhotra, Anil K. ^{[29
,30
,31
]}

Purcell, Shaun ^{[18
]}

Dudbridge, Frank ^{[32
]}

Neale, Benjamin M. ^{[18
]}

Rossin, Lizzy ^{[2
]}

Visscher, Peter M. ^{[33
]}

Posthuma, Danielle ^{[34
,35
]}

Ruderfer, Douglas M. ^{[2
]}

Fanous, Ayman ^{[5
,36
,37
]}

Stefansson, Hreinn ^{[38
]}

Steinberg, Stacy ^{[38
]}

Mowry, Bryan J. ^{[39
,40
]}

Golimbet, Vera ^{[41
]}

De Hert, Marc ^{[42
]}

Jonsson, Erik G. ^{[43
]}

Bitter, Istvan ^{[44
]}

Pietilainen, Olli P. H. ^{[45
,46
]}

Collier, David A. ^{[47
]}

Tosato, Sarah ^{[48
]}

Agartz, Ingrid ^{[16
,49
]}

Albus, Margot ^{[50
]}

Alexander, Madeline ^{[7
]}

Amdur, Richard L. ^{[36
,37
]}

Amin, Farooq ^{[51
,52
]}

Bass, Nicholas ^{[24
]}

Bergen, Sarah E. ^{[2
]}

Black, Donald W. ^{[53
]}

Borglum, Anders D. ^{[54
,55
]}

Brown, Matthew A. ^{[56
]}

Bruggeman, Richard ^{[57
]}

Buccola, Nancy G. ^{[58
]}

机构：

[1] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA

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

[3] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA

[4] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[5] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA USA

[6] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA

[7] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[8] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[9] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Gen, Sch Med, Cardiff, S Glam, Wales

[10] Cardiff Univ, Dept Psychol Med & Neurol, Sch Med, Cardiff, S Glam, Wales

[11] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[12] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[13] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[14] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA

[15] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[16] Univ Oslo, Inst Clin Med, Psychiat Sect, Oslo, Norway

[17] Oslo Univ Hosp, Dept Psychiat, Oslo, Norway

[18] Broad Inst, Cambridge, MA USA

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

[20] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany

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

[22] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland

[23] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Dublin, Ireland

[24] UCL, Sch Med, Windeyer Inst Med Sci, Mol Psychiat Lab,Res Dept Mental Hlth Sci, London W1N 8AA, England

[25] Copenhagen Univ Hosp, Inst Biol Psychiat, Mental Hlth Ctr MHC Sct Hans, Roskilde, Denmark

[26] Univ Munich, Dept Psychiat, D-8000 Munich, Germany

[27] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland

[28] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA

[29] Zucker Hillside Hosp, Div N Shore Long Isl Jewish Hlth Syst, Div Res, Dept Psychiat, Glen Oaks, NY USA

[30] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA

[31] Yeshiva Univ, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, New York, NY 10033 USA

[32] London Sch Hyg & Trop Med, Dept Non Communicable Dis Epidemiol, London WC1, England

[33] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia

[34] Vrije Univ Amsterdam, CNCR, Dept Funct Gen, Amsterdam, Netherlands

[35] Vrije Univ Amsterdam Med Ctr, Dept Med Genom, Amsterdam, Netherlands

[36] Vet Affairs Med Ctr, Washington, DC 20422 USA

[37] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA

[38] deCODE Genet, Reykjavik, Iceland

[39] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[40] Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia

[41] Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia

[42] Katholieke Univ Leuven, Univ Psychiat Ctr, Kortenberg, Belgium

[43] Karolinska Hosp & Inst, Human Brain Informat HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden

[44] Semmelweis Univ, Dept Psychiat & Psychotherapy, Budapest, Hungary

[45] Univ Helsinki, FIMM, Helsinki, Finland

[46] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[47] Kings Coll London, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England

[48] Univ Verona, Sect Psychiat & Clin Psychol, I-37100 Verona, Italy

[49] Diakonhjemmet Hosp, Dept Res, Oslo, Norway

[50] State Mental Hosp, Haar, Germany

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

美国国家卫生研究院;

关键词：

COMMON SNPS EXPLAIN; BIPOLAR DISORDER; HUMAN HEIGHT; LARGE PROPORTION; MICRORNA; VARIANTS; SUSCEPTIBILITY; HERITABILITY; INDIVIDUALS; ANCESTRY;

D O I：

10.1038/ng.940

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

引用

页码：969 / 976

页数：8

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