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

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; August B Smit; Hreinn Stefansson; Francis A O'Neill; Multicenter Genetic Studies of Schizophrenia Consortium

doi:10.1038/ng.2742

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

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 BorglumBrendan 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, August B Smit, Hreinn Stefansson, Francis A O'Neill, Multicenter Genetic Studies of Schizophrenia Consortium

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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)	1150-1159
Journal	Nature Genetics
Volume	45
DOIs	https://doi.org/10.1038/ng.2742
Publication status	Published - 25 Aug 2013

Bibliographical note

This is the second large study using Genome-Wide Association using data from the ICCSS and the RPGI sample to uncover genes for schizophrenia. These two samples together with other worldwide samples were used to find 13new loci for schizophrenia. This represents a significant breakthrough in understanding some of the mechanisms underlying risk for schizophrenia. I helped write the grants that helped with the collection of the data,I contributed towards the analysis and the write up of the paper.

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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., Bettella, F., ... Multicenter Genetic Studies of Schizophrenia Consortium (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45, 1150-1159. https://doi.org/10.1038/ng.2742

Ripke, Stephan ; O'Dushlaine, Colm ; Chambert, Kimberly ; Moran, Jennifer L ; Kähler, Anna K ; Akterin, Susanne ; Bergen, Sarah E ; Collins, Ann L ; Crowley, James J ; Fromer, Menachem ; Kim, Yunjung ; Lee, Sang Hong ; Magnusson, Patrik K E ; Sanchez, Nick ; Stahl, Eli A ; Williams, Stephanie ; Wray, Naomi R ; Xia, Kai ; Bettella, Francesco ; Borglum, Anders D ; Bulik-Sullivan, Brendan K ; Cormican, Paul ; Craddock, Nick ; de Leeuw, Christiaan ; Durmishi, Naser ; Gill, Michael ; Golimbet, Vera ; Hamshere, Marian L ; Holmans, Peter ; Hougaard, David M ; Kendler, Kenneth S ; Lin, Kuang ; Morris, Derek W ; Mors, Ole ; Mortensen, Preben B ; Neale, Benjamin M ; O'Neill, Francis A ; Owen, Michael J ; Milovancevic, Milica Pejovic ; Posthuma, Danielle ; Powell, John ; Richards, Alexander L ; Riley, Brien P ; Ruderfer, Douglas ; Rujescu, Dan ; Sigurdsson, Engilbert ; Silagadze, Teimuraz ; Smit, August B ; Stefansson, Hreinn ; O'Neill, Francis A ; Multicenter Genetic Studies of Schizophrenia Consortium. / Genome-wide association analysis identifies 13 new risk loci for schizophrenia. In: Nature Genetics. 2013 ; Vol. 45. pp. 1150-1159.

@article{a2910970a09a4ac3bfb27565002450fb,

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.",

author = "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 Smit, {August B} and Hreinn Stefansson and O'Neill, {Francis A} and {Multicenter Genetic Studies of Schizophrenia Consortium}",

note = "This is the second large study using Genome-Wide Association using data from the ICCSS and the RPGI sample to uncover genes for schizophrenia. These two samples together with other worldwide samples were used to find 13new loci for schizophrenia. This represents a significant breakthrough in understanding some of the mechanisms underlying risk for schizophrenia. I helped write the grants that helped with the collection of the data,I contributed towards the analysis and the write up of the paper.",

year = "2013",

month = aug,

day = "25",

doi = "10.1038/ng.2742",

language = "English",

volume = "45",

pages = "1150--1159",

journal = "Nature Genetics",

issn = "1061-4036",

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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, Smit, AB, Stefansson, H, O'Neill, FA & Multicenter Genetic Studies of Schizophrenia Consortium 2013, 'Genome-wide association analysis identifies 13 new risk loci for schizophrenia', Nature Genetics, vol. 45, pp. 1150-1159. https://doi.org/10.1038/ng.2742

Genome-wide association analysis identifies 13 new risk loci for schizophrenia. / Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah E; Collins, Ann L; Crowley, James J; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K E; Sanchez, Nick; Stahl, Eli A; Williams, Stephanie; Wray, Naomi R; Xia, Kai; Bettella, Francesco; Borglum, Anders D; Bulik-Sullivan, Brendan K; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L; Holmans, Peter; Hougaard, David M; Kendler, Kenneth S; Lin, Kuang; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; O'Neill, Francis A; Owen, Michael J; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L; Riley, Brien P; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B; Stefansson, Hreinn; O'Neill, Francis A; Multicenter Genetic Studies of Schizophrenia Consortium.

In: Nature Genetics, Vol. 45, 25.08.2013, p. 1150-1159.

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

TY - JOUR

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

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 - Smit, August B

AU - Stefansson, Hreinn

AU - O'Neill, Francis A

AU - Multicenter Genetic Studies of Schizophrenia Consortium

N1 - This is the second large study using Genome-Wide Association using data from the ICCSS and the RPGI sample to uncover genes for schizophrenia. These two samples together with other worldwide samples were used to find 13new loci for schizophrenia. This represents a significant breakthrough in understanding some of the mechanisms underlying risk for schizophrenia. I helped write the grants that helped with the collection of the data,I contributed towards the analysis and the write up of the paper.

PY - 2013/8/25

Y1 - 2013/8/25

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.

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DO - 10.1038/ng.2742

M3 - Article

C2 - 23974872

VL - 45

SP - 1150

EP - 1159

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -

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

Abstract

Bibliographical note

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