Genome-wide association study identifies five new schizophrenia loci

Stephan Ripke, Alan R Sanders, Kenneth S Kendler, Douglas F Levinson, Pamela Sklar, Peter A Holmans, Dan-Yu Lin, Jubao Duan, Roel A Ophoff, Ole A Andreassen, Edward Scolnick, Sven Cichon, David St Clair, Aiden Corvin, Hugh Gurling, Thomas Werge, Dan Rujescu, Douglas H R Blackwood, Carlos N Pato, Anil K Malhotra & 31 others Shaun Purcell, Frank Dudbridge, Benjamin M Neale, Lizzy Rossin, Peter M Visscher, Danielle Posthuma, Douglas M Ruderfer, Ayman Fanous, Hreinn Stefansson, Stacy Steinberg, Bryan J Mowry, Vera Golimbet, Marc De Hert, Erik G Jönsson, István Bitter, Olli P H Pietiläinen, David A Collier, Sarah Tosato, Ingrid Agartz, Margot Albus, Madeline Alexander, Richard L Amdur, Farooq Amin, Nicholas Bass, Sarah E Bergen, Donald W Black, Anders D Børglum, Matthew A Brown, Richard Bruggeman, Nancy G Buccola, Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium

Research output: Contribution to journalArticle

1198 Citations (Scopus)

Abstract

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 × 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 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).
Original languageEnglish
Pages (from-to)969-976
Number of pages8
JournalNature Genetics
Volume43
Issue number10
Early online date18 Sep 2011
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Genome-Wide Association Study
Schizophrenia
MicroRNAs
Genome
Internal-External Control
Bipolar Disorder
Introns

Keywords

  • alleles
  • bipolar disorder
  • case-control studies
  • European continental ancestry group
  • female
  • gene dosage
  • gene expression regulation
  • genetic loci
  • genetic predisposition to disease
  • genome, human
  • genome-wide association study
  • haplotypes
  • humans
  • linkage disequilibrium
  • logistic models
  • male
  • microRNAs
  • mutation
  • polymorphism, single nucleotide
  • schizophrenia

Cite this

Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., ... Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969-976. https://doi.org/10.1038/ng.940

Genome-wide association study identifies five new schizophrenia loci. / Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S; Levinson, Douglas F; Sklar, Pamela; Holmans, Peter A; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A; Andreassen, Ole A; Scolnick, Edward; Cichon, Sven; St Clair, David; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H R; Pato, Carlos N; Malhotra, Anil K; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M; Rossin, Lizzy; Visscher, Peter M; Posthuma, Danielle; Ruderfer, Douglas M; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J; Golimbet, Vera; De Hert, Marc; Jönsson, Erik G; Bitter, István; Pietiläinen, Olli P H; Collier, David A; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E; Black, Donald W; Børglum, Anders D; Brown, Matthew A; Bruggeman, Richard; Buccola, Nancy G; Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium.

In: Nature Genetics, Vol. 43, No. 10, 10.2011, p. 969-976.

Research output: Contribution to journalArticle

Ripke, S, Sanders, AR, Kendler, KS, Levinson, DF, Sklar, P, Holmans, PA, Lin, D-Y, Duan, J, Ophoff, RA, Andreassen, OA, Scolnick, E, Cichon, S, St Clair, D, Corvin, A, Gurling, H, Werge, T, Rujescu, D, Blackwood, DHR, Pato, CN, Malhotra, AK, Purcell, S, Dudbridge, F, Neale, BM, Rossin, L, Visscher, PM, Posthuma, D, Ruderfer, DM, Fanous, A, Stefansson, H, Steinberg, S, Mowry, BJ, Golimbet, V, De Hert, M, Jönsson, EG, Bitter, I, Pietiläinen, OPH, Collier, DA, Tosato, S, Agartz, I, Albus, M, Alexander, M, Amdur, RL, Amin, F, Bass, N, Bergen, SE, Black, DW, Børglum, AD, Brown, MA, Bruggeman, R, Buccola, NG & Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium 2011, 'Genome-wide association study identifies five new schizophrenia loci' Nature Genetics, vol. 43, no. 10, pp. 969-976. https://doi.org/10.1038/ng.940
Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA et al. Genome-wide association study identifies five new schizophrenia loci. Nature Genetics. 2011 Oct;43(10):969-976. https://doi.org/10.1038/ng.940
Ripke, Stephan ; Sanders, Alan R ; Kendler, Kenneth S ; Levinson, Douglas F ; Sklar, Pamela ; Holmans, Peter A ; Lin, Dan-Yu ; Duan, Jubao ; Ophoff, Roel A ; Andreassen, Ole A ; Scolnick, Edward ; Cichon, Sven ; St Clair, David ; Corvin, Aiden ; Gurling, Hugh ; Werge, Thomas ; Rujescu, Dan ; Blackwood, Douglas H R ; Pato, Carlos N ; Malhotra, Anil K ; Purcell, Shaun ; Dudbridge, Frank ; Neale, Benjamin M ; Rossin, Lizzy ; Visscher, Peter M ; Posthuma, Danielle ; Ruderfer, Douglas M ; Fanous, Ayman ; Stefansson, Hreinn ; Steinberg, Stacy ; Mowry, Bryan J ; Golimbet, Vera ; De Hert, Marc ; Jönsson, Erik G ; Bitter, István ; Pietiläinen, Olli P H ; Collier, David A ; Tosato, Sarah ; Agartz, Ingrid ; Albus, Margot ; Alexander, Madeline ; Amdur, Richard L ; Amin, Farooq ; Bass, Nicholas ; Bergen, Sarah E ; Black, Donald W ; Børglum, Anders D ; Brown, Matthew A ; Bruggeman, Richard ; Buccola, Nancy G ; Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. / Genome-wide association study identifies five new schizophrenia loci. In: Nature Genetics. 2011 ; Vol. 43, No. 10. pp. 969-976.
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AU - Sanders, Alan R

AU - Kendler, Kenneth S

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AU - Sklar, Pamela

AU - Holmans, Peter A

AU - Lin, Dan-Yu

AU - Duan, Jubao

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AU - Pato, Carlos N

AU - Malhotra, Anil K

AU - Purcell, Shaun

AU - Dudbridge, Frank

AU - Neale, Benjamin M

AU - Rossin, Lizzy

AU - Visscher, Peter M

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AU - Ruderfer, Douglas M

AU - Fanous, Ayman

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Mowry, Bryan J

AU - Golimbet, Vera

AU - De Hert, Marc

AU - Jönsson, Erik G

AU - Bitter, István

AU - Pietiläinen, Olli P H

AU - Collier, David A

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KW - case-control studies

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KW - female

KW - gene dosage

KW - gene expression regulation

KW - genetic loci

KW - genetic predisposition to disease

KW - genome, human

KW - genome-wide association study

KW - haplotypes

KW - humans

KW - linkage disequilibrium

KW - logistic models

KW - male

KW - microRNAs

KW - mutation

KW - polymorphism, single nucleotide

KW - schizophrenia

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DO - 10.1038/ng.940

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JO - Nature Genetics

JF - Nature Genetics

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