Biological insights from 108 schizophrenia-associated genetic loci

Stephan Ripke; Benjamin M. Neale; Aiden Corvin; James T. R. Walters; Kai-How Farh; Peter A. Holmans; Phil Lee; Brendan Bulik-Sullivan; David A. Collier; Hailiang Huang; Tune H. Pers; Ingrid Agartz; Esben Agerbo; Margot Albus; Madeline Alexander; Farooq Amin; Silviu A. Bacanu; Martin Begemann; Richard A. Belliveau; Judit Bene; Sarah E. Bergen; Elizabeth Bevilacqua; Tim B. Bigdeli; Donald W. Black; Richard Bruggeman; Nancy G. Buccola; Randy L. Buckner; William Byerley; Wiepke Cahn; Guiqing Cai; Dominique Campion; Rita M. Cantor; Vaughan J. Carr; Noa Carrera; Stanley V. Catts; Kimberly D. Chambert; Raymond C. K. Chan; Ronald Y. L. Chen; Eric Y. H. Chen; Wei Cheng; Eric F. C. Cheung; Siow Ann Chong; C. Robert Cloninger; David Cohen; Nadine Cohen; Paul Cormican; Nick Craddock; Inez Myin-Germeys; Jim Van Os; Qiang Wang; Author collaboration

doi:10.1038/nature13595

Biological insights from 108 schizophrenia-associated genetic loci

Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T. R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit BeneSarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C. K. Chan, Ronald Y. L. Chen, Eric Y. H. Chen, Wei Cheng, Eric F. C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, Inez Myin-Germeys, Jim Van Os, Qiang Wang, Author collaboration

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Original language	English
Article number	421
Number of pages	17
Journal	Nature
Volume	511
Issue number	7510
DOIs	https://doi.org/10.1038/nature13595
Publication status	Published - 24 Jul 2014

Keywords

Genome-wide association
Common variants
Conferring risk
Mutations

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10.1038/nature13595

Cite this

Ripke, S., Neale, B. M., Corvin, A., Walters, J. T. R., Farh, K.-H., Holmans, P. A., Lee, P., Bulik-Sullivan, B., Collier, D. A., Huang, H., Pers, T. H., Agartz, I., Agerbo, E., Albus, M., Alexander, M., Amin, F., Bacanu, S. A., Begemann, M., Belliveau, R. A., ... Author collaboration (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), Article 421. https://doi.org/10.1038/nature13595

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title = "Biological insights from 108 schizophrenia-associated genetic loci",

abstract = "Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.",

keywords = "Genome-wide association, Common variants, Conferring risk, Mutations",

author = "Stephan Ripke and Neale, {Benjamin M.} and Aiden Corvin and Walters, {James T. R.} and Kai-How Farh and Holmans, {Peter A.} and Phil Lee and Brendan Bulik-Sullivan and Collier, {David A.} and Hailiang Huang and Pers, {Tune H.} and Ingrid Agartz and Esben Agerbo and Margot Albus and Madeline Alexander and Farooq Amin and Bacanu, {Silviu A.} and Martin Begemann and Belliveau, {Richard A.} and Judit Bene and Bergen, {Sarah E.} and Elizabeth Bevilacqua and Bigdeli, {Tim B.} and Black, {Donald W.} and Richard Bruggeman and Buccola, {Nancy G.} and Buckner, {Randy L.} and William Byerley and Wiepke Cahn and Guiqing Cai and Dominique Campion and Cantor, {Rita M.} and Carr, {Vaughan J.} and Noa Carrera and Catts, {Stanley V.} and Chambert, {Kimberly D.} and Chan, {Raymond C. K.} and Chen, {Ronald Y. L.} and Chen, {Eric Y. H.} and Wei Cheng and Cheung, {Eric F. C.} and Chong, {Siow Ann} and Cloninger, {C. Robert} and David Cohen and Nadine Cohen and Paul Cormican and Nick Craddock and Inez Myin-Germeys and {Van Os}, Jim and Qiang Wang and {Author collaboration}",

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Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Myin-Germeys, I, Van Os, J, Wang, Q & Author collaboration 2014, 'Biological insights from 108 schizophrenia-associated genetic loci', Nature, vol. 511, no. 7510, 421. https://doi.org/10.1038/nature13595

TY - JOUR

T1 - Biological insights from 108 schizophrenia-associated genetic loci

AU - Ripke, Stephan

AU - Neale, Benjamin M.

AU - Corvin, Aiden

AU - Walters, James T. R.

AU - Farh, Kai-How

AU - Holmans, Peter A.

AU - Lee, Phil

AU - Bulik-Sullivan, Brendan

AU - Collier, David A.

AU - Huang, Hailiang

AU - Pers, Tune H.

AU - Agartz, Ingrid

AU - Agerbo, Esben

AU - Albus, Margot

AU - Alexander, Madeline

AU - Amin, Farooq

AU - Bacanu, Silviu A.

AU - Begemann, Martin

AU - Belliveau, Richard A.

AU - Bene, Judit

AU - Bergen, Sarah E.

AU - Bevilacqua, Elizabeth

AU - Bigdeli, Tim B.

AU - Black, Donald W.

AU - Bruggeman, Richard

AU - Buccola, Nancy G.

AU - Buckner, Randy L.

AU - Byerley, William

AU - Cahn, Wiepke

AU - Cai, Guiqing

AU - Campion, Dominique

AU - Cantor, Rita M.

AU - Carr, Vaughan J.

AU - Carrera, Noa

AU - Catts, Stanley V.

AU - Chambert, Kimberly D.

AU - Chan, Raymond C. K.

AU - Chen, Ronald Y. L.

AU - Chen, Eric Y. H.

AU - Cheng, Wei

AU - Cheung, Eric F. C.

AU - Chong, Siow Ann

AU - Cloninger, C. Robert

AU - Cohen, David

AU - Cohen, Nadine

AU - Cormican, Paul

AU - Craddock, Nick

AU - Myin-Germeys, Inez

AU - Van Os, Jim

AU - Wang, Qiang

AU - Author collaboration

PY - 2014/7/24

Y1 - 2014/7/24

N2 - Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

AB - Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

KW - Genome-wide association

KW - Common variants

KW - Conferring risk

KW - Mutations

U2 - 10.1038/nature13595

DO - 10.1038/nature13595

M3 - Article

C2 - 25056061

SN - 0028-0836

VL - 511

JO - Nature

JF - Nature

IS - 7510

M1 - 421

ER -