Genome-wide association analysis identifies 13 new risk loci for schizophrenia

被引：1142

作者：

Ripke, Stephan ^{[1
,2
]}

O'Dushlaine, Colm ^{[2
]}

Chambert, Kimberly ^{[2
]}

Moran, Jennifer L. ^{[2
]}

Kaehler, Anna K. ^{[3
,4
,5
]}

Akterin, Susanne ^{[4
]}

Bergen, Sarah E. ^{[4
]}

Collins, Ann L. ^{[3
]}

Crowley, James J. ^{[3
]}

Fromer, Menachem ^{[1
,2
,6
]}

Kim, Yunjung ^{[3
]}

Lee, Sang Hong ^{[7
]}

Magnusson, Patrik K. E. ^{[4
]}

Sanchez, Nick ^{[2
]}

Stahl, Eli A. ^{[6
]}

Williams, Stephanie ^{[3
]}

Wray, Naomi R. ^{[7
]}

Xia, Kai ^{[8
]}

Bettella, Francesco ^{[9
]}

Borglum, Anders D. ^{[10
,11
,12
,13
]}

Bulik-Sullivan, Brendan K. ^{[1
]}

Cormican, Paul ^{[14
]}

Craddock, Nick ^{[15
]}

de Leeuw, Christiaan ^{[16
,17
,18
]}

Durmishi, Naser ^{[19
]}

Gill, Michael ^{[14
,20
]}

Golimbet, Vera ^{[21
]}

Hamshere, Marian L. ^{[15
]}

Holmans, Peter ^{[15
]}

Hougaard, David M. ^{[22
]}

Kendler, Kenneth S. ^{[23
,24
]}

Lin, Kuang ^{[25
]}

Morris, Derek W. ^{[14
,20
]}

Mors, Ole ^{[12
,13
,26
]}

Mortensen, Preben B. ^{[12
,13
,27
]}

Neale, Benjamin M. ^{[1
,2
]}

O'Neill, Francis A. ^{[28
]}

Owen, Michael J. ^{[15
]}

Milovancevic, Milica Pejovic ^{[29
]}

Posthuma, Danielle ^{[16
,17
,30
]}

Powell, John ^{[25
,31
]}

Richards, Alexander L. ^{[15
]}

Riley, Brien P. ^{[23
,24
,32
]}

Ruderfer, Douglas ^{[6
]}

Rujescu, Dan ^{[33
,34
]}

Sigurdsson, Engilbert ^{[35
]}

Silagadze, Teimuraz ^{[36
]}

Smit, August B. ^{[37
,38
]}

Stefansson, Hreinn ^{[9
]}

Steinberg, Stacy ^{[9
]}

机构：

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

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

[3] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

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

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

[6] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA

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

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

[9] deCODE Genet, Reykjavik, Iceland

[10] Aarhus Univ Hosp, Risskov, Denmark

[11] Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark

[12] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark

[13] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark

[14] Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland

[15] Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales

[16] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands

[17] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

[18] Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands

[19] Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia

[20] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland

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

[22] Statens Serum Inst, DK-2300 Copenhagen, Denmark

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

[24] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[25] Kings Coll London, Inst Psychiat, London, England

[26] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark

[27] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark

[28] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland

[29] Univ Belgrade, Fac Med, Belgrade, Serbia

[30] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands

[31] Kings Coll London, Dept Neurosci, London, England

[32] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA

[33] Univ Halle, Dept Psychiat, Halle, Germany

[34] Univ Munich, Dept Psychiat, D-80539 Munich, Germany

[35] Univ Iceland, Dept Psychiat, Reykjavik, Iceland

[36] Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Georgia

[37] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands

[38] Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands

[39] Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland

[40] Univ Verona, Sect Psychiat, I-37100 Verona, Italy

[41] UCL, Inst Cognit Neurosci, London, England

[42] UCL, Mental Hlth Sci Unit, London, England

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

[44] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 10期

基金：

瑞典研究理事会; 英国惠康基金;

关键词：

DEPENDENT CALCIUM-CHANNELS; DE-NOVO; BIPOLAR DISORDER; COMMON VARIANTS; GENE-EXPRESSION; METAANALYSIS; MICRORNA; SUSCEPTIBILITY; PARTICIPATION; INDIVIDUALS;

D O I：

10.1038/ng.2742

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

引用

页码：1150 / +

页数：12

共 98 条

[1] Hundreds of variants clustered in genomic loci and biological pathways affect human height [J].

Allen, Hana Lango ;

Estrada, Karol ;

Lettre, Guillaume ;

Berndt, Sonja I. ;

Weedon, Michael N. ;

Rivadeneira, Fernando ;

Willer, Cristen J. ;

Jackson, Anne U. ;

Vedantam, Sailaja ;

Raychaudhuri, Soumya ;

Ferreira, Teresa ;

Wood, Andrew R. ;

Weyant, Robert J. ;

Segre, Ayellet V. ;

Speliotes, Elizabeth K. ;

Wheeler, Eleanor ;

Soranzo, Nicole ;

Park, Ju-Hyun ;

Yang, Jian ;

Gudbjartsson, Daniel ;

Heard-Costa, Nancy L. ;

Randall, Joshua C. ;

Qi, Lu ;

Smith, Albert Vernon ;

Maegi, Reedik ;

Pastinen, Tomi ;

Liang, Liming ;

Heid, Iris M. ;

Luan, Jian'an ;

Thorleifsson, Gudmar ;

Winkler, Thomas W. ;

Goddard, Michael E. ;

Lo, Ken Sin ;

Palmer, Cameron ;

Workalemahu, Tsegaselassie ;

Aulchenko, Yurii S. ;

Johansson, Asa ;

Zillikens, M. Carola ;

Feitosa, Mary F. ;

Esko, Tonu ;

Johnson, Toby ;

Ketkar, Shamika ;

Kraft, Peter ;

Mangino, Massimo ;

Prokopenko, Inga ;

Absher, Devin ;

Albrecht, Eva ;

Ernst, Florian ;

Glazer, Nicole L. ;

Hayward, Caroline .

NATURE, 2010, 467 (7317) :832-838

[2] Appendectomy and protection against ulcerative colitis. [J].

Andersson, RE ;

Olaison, G ;

Tysk, C ;

Ekbom, A .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (11) :808-814

[3]

[Anonymous], 1967, INT CLASS DIS

[4]

[Anonymous], 1992, INT CLASS DIS

[5]

[Anonymous], 1978, INT CLASS DIS

[6]

[Anonymous], [No title captured], DOI DOI 10.1016/j.ajhg.2011.01.017

[7] Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder [J].

Bergen, S. E. ;

O'Dushlaine, C. T. ;

Ripke, S. ;

Lee, P. H. ;

Ruderfer, D. M. ;

Akterin, S. ;

Moran, J. L. ;

Chambert, K. D. ;

Handsaker, R. E. ;

Backlund, L. ;

Osby, U. ;

McCarroll, S. ;

Landen, M. ;

Scolnick, E. M. ;

Magnusson, P. K. E. ;

Lichtenstein, P. ;

Hultman, C. M. ;

Purcell, S. M. ;

Sklar, P. ;

Sullivan, P. F. .

MOLECULAR PSYCHIATRY, 2012, 17 (09) :880-886

[8] Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting [J].

Betancur, Catalina .

BRAIN RESEARCH, 2011, 1380 :42-77

[9] The I-II loop of the Ca2+ channel α1 subunit contains an endoplasmic reticulum retention signal antagonized by the β subunit [J].

Bichet, D ;

Cornet, V ;

Geib, S ;

Carlier, E ;

Volsen, S ;

Hoshi, T ;

Mori, Y ;

De Waard, M .

NEURON, 2000, 25 (01) :177-190

[10] Voltage-gated calcium channels in genetic diseases [J].

Bidaud, Isabelle ;

Mezghrani, Alexandre ;

Swayne, Leigh Anne ;

Monteil, Arnaud ;

Lory, Philippe .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2006, 1763 (11) :1169-1174

← 1 2 3 4 5 6 7 8 9 10 →