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

Multicenter Genetic Studies of Schizophrenia Consortium; Stephan Ripke; Colm O'Dushlaine; Kimberly Chambert; Jennifer L Moran; Anna K Kähler; Susanne Akterin; Sarah E Bergen; Ann L Collins; James J Crowley; Menachem Fromer; Yunjung Kim; Sang Hong Lee; Patrik K E Magnusson; Nick Sanchez; Eli A Stahl; Stephanie Williams; Naomi R Wray; Kai Xia; Francesco Bettella; Anders D Borglum; Brendan K Bulik-Sullivan; Paul Cormican; Nick Craddock; Christiaan de Leeuw; Naser Durmishi; Michael Gill; Vera Golimbet; Marian L Hamshere; Peter Holmans; David M Hougaard; Kenneth S Kendler; Kuang Lin; Derek W Morris; Ole Mors; Preben B Mortensen; Benjamin M Neale; Francis A O'Neill; Michael J Owen; Milica Pejovic Milovancevic; Danielle Posthuma; John Powell; Alexander L Richards; Brien P Riley; Douglas Ruderfer; Dan Rujescu; Engilbert Sigurdsson; Teimuraz Silagadze; Jeremy Hall; Stephen Lawrie; Andrew McIntosh

doi:10.1038/ng.2742

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

Multicenter Genetic Studies of Schizophrenia Consortium, Stephan Ripke, Colm O'Dushlaine, Kimberly Chambert, Jennifer L Moran, Anna K Kähler, Susanne Akterin, Sarah E Bergen, Ann L Collins, James J Crowley, Menachem Fromer, Yunjung Kim, Sang Hong Lee, Patrik K E Magnusson, Nick Sanchez, Eli A Stahl, Stephanie Williams, Naomi R Wray, Kai Xia, Francesco BettellaAnders D Borglum, Brendan K Bulik-Sullivan, Paul Cormican, Nick Craddock, Christiaan de Leeuw, Naser Durmishi, Michael Gill, Vera Golimbet, Marian L Hamshere, Peter Holmans, David M Hougaard, Kenneth S Kendler, Kuang Lin, Derek W Morris, Ole Mors, Preben B Mortensen, Benjamin M Neale, Francis A O'Neill, Michael J Owen, Milica Pejovic Milovancevic, Danielle Posthuma, John Powell, Alexander L Richards, Brien P Riley, Douglas Ruderfer, Dan Rujescu, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy Hall, Stephen Lawrie, Andrew McIntosh

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

Abstract

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.

Original language	English
Pages (from-to)	1150-9
Number of pages	10
Journal	Nature Genetics
Volume	45
Issue number	10
DOIs	https://doi.org/10.1038/ng.2742
Publication status	Published - Oct 2013

Keywords / Materials (for Non-textual outputs)

Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Schizophrenia
Sweden

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10.1038/ng.2742

Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Published in final edited form as: Nat Genet. Oct 2013; 45(10): 10.1038/ng.2742.
Accepted author manuscript, 836 KB

http://www.nature.com/ng/journal/v45/n10/full/ng.2742.html

Medial temporal lobe function & associative memory formation in schizophrenia
Hall, J. (Principal Investigator)
MRC
1/01/07 → 30/07/10
Project: Research

Cite this

Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., Collins, A. L., Crowley, J. J., Fromer, M., Kim, Y., Lee, S. H., Magnusson, P. K. E., Sanchez, N., Stahl, E. A., Williams, S., Wray, N. R., Xia, K., ... McIntosh, A. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150-9. https://doi.org/10.1038/ng.2742

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title = "Genome-wide association analysis identifies 13 new risk loci for schizophrenia",

abstract = "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.",

keywords = "Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Schizophrenia, Sweden",

author = "{Multicenter Genetic Studies of Schizophrenia Consortium} and Stephan Ripke and Colm O'Dushlaine and Kimberly Chambert and Moran, {Jennifer L} and K{\"a}hler, {Anna K} and Susanne Akterin and Bergen, {Sarah E} and Collins, {Ann L} and Crowley, {James J} and Menachem Fromer and Yunjung Kim and Lee, {Sang Hong} and Magnusson, {Patrik K E} and Nick Sanchez and Stahl, {Eli A} and Stephanie Williams and Wray, {Naomi R} and Kai Xia and Francesco Bettella and Borglum, {Anders D} and Bulik-Sullivan, {Brendan K} and Paul Cormican and Nick Craddock and {de Leeuw}, Christiaan and Naser Durmishi and Michael Gill and Vera Golimbet and Hamshere, {Marian L} and Peter Holmans and Hougaard, {David M} and Kendler, {Kenneth S} and Kuang Lin and Morris, {Derek W} and Ole Mors and Mortensen, {Preben B} and Neale, {Benjamin M} and O'Neill, {Francis A} and Owen, {Michael J} and Milovancevic, {Milica Pejovic} and Danielle Posthuma and John Powell and Richards, {Alexander L} and Riley, {Brien P} and Douglas Ruderfer and Dan Rujescu and Engilbert Sigurdsson and Teimuraz Silagadze and Jeremy Hall and Stephen Lawrie and Andrew McIntosh",

year = "2013",

month = oct,

doi = "10.1038/ng.2742",

language = "English",

volume = "45",

pages = "1150--9",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

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Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PKE, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O'Neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Hall, J, Lawrie, S & McIntosh, A 2013, 'Genome-wide association analysis identifies 13 new risk loci for schizophrenia', Nature Genetics, vol. 45, no. 10, pp. 1150-9. https://doi.org/10.1038/ng.2742

TY - JOUR

T1 - Genome-wide association analysis identifies 13 new risk loci for schizophrenia

AU - Multicenter Genetic Studies of Schizophrenia Consortium

AU - Ripke, Stephan

AU - O'Dushlaine, Colm

AU - Chambert, Kimberly

AU - Moran, Jennifer L

AU - Kähler, Anna K

AU - Akterin, Susanne

AU - Bergen, Sarah E

AU - Collins, Ann L

AU - Crowley, James J

AU - Fromer, Menachem

AU - Kim, Yunjung

AU - Lee, Sang Hong

AU - Magnusson, Patrik K E

AU - Sanchez, Nick

AU - Stahl, Eli A

AU - Williams, Stephanie

AU - Wray, Naomi R

AU - Xia, Kai

AU - Bettella, Francesco

AU - Borglum, Anders D

AU - Bulik-Sullivan, Brendan K

AU - Cormican, Paul

AU - Craddock, Nick

AU - de Leeuw, Christiaan

AU - Durmishi, Naser

AU - Gill, Michael

AU - Golimbet, Vera

AU - Hamshere, Marian L

AU - Holmans, Peter

AU - Hougaard, David M

AU - Kendler, Kenneth S

AU - Lin, Kuang

AU - Morris, Derek W

AU - Mors, Ole

AU - Mortensen, Preben B

AU - Neale, Benjamin M

AU - O'Neill, Francis A

AU - Owen, Michael J

AU - Milovancevic, Milica Pejovic

AU - Posthuma, Danielle

AU - Powell, John

AU - Richards, Alexander L

AU - Riley, Brien P

AU - Ruderfer, Douglas

AU - Rujescu, Dan

AU - Sigurdsson, Engilbert

AU - Silagadze, Teimuraz

AU - Hall, Jeremy

AU - Lawrie, Stephen

AU - McIntosh, Andrew

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia

KW - Sweden

U2 - 10.1038/ng.2742

DO - 10.1038/ng.2742

M3 - Article

C2 - 23974872

SN - 1061-4036

VL - 45

SP - 1150

EP - 1159

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Medial temporal lobe function & associative memory formation in schizophrenia

Cite this