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

Stephan Ripke; Colm O'dushlaine; Kimberly Chambert; Jennifer L Moran; Anna K K??hler; 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; Kuang Lin; Benjamin M Neale; John Powell; Brien P Riley; James T Walters; Multicenter Genetic Studies of Schizophrenia Consortium; Psychosis Endophenotypes International Consortium; Wellcome Trust Case Consortium 2; Shaun Purcell

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 K??hler, 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, Kuang Lin, Benjamin M Neale, John Powell, Brien P Riley, James T Walters, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Consortium 2, Shaun Purcell

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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
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

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827979/

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Ripke, S., O'dushlaine, C., Chambert, K., Moran, J. L., K??hler, 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., ... Purcell, S. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150-1159. https://doi.org/10.1038/ng.2742

@article{ee7dd150a41848ae8773c4e6b0f3dd5f,

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??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 Kuang Lin and Neale, {Benjamin M} and John Powell and Riley, {Brien P} and Walters, {James T} and Riley, {Brien P} and Arranz, {Maria J} and David Collier and Conrad Iyegbe and Lewis, {Cathryn M} and Kuang Lin and Ignacio Mata and Murray, {Robin M} and John Powell and {Van Os}, Jim and Muriel Walshe and Mathew, {Christopher G} and Robert Plomin and Trembath, {Richard C} and Viswanathan, {Ananth C} and Emma Gray and Paul Weston and Mathew, {Christopher G} and {Multicenter Genetic Studies of Schizophrenia Consortium} and {Psychosis Endophenotypes International Consortium} and {Wellcome Trust Case Consortium 2} and Shaun Purcell",

year = "2013",

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doi = "10.1038/ng.2742",

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volume = "45",

pages = "1150--1159",

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Ripke, S, O'dushlaine, C, Chambert, K, Moran, JL, K??hler, 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, Lin, K , Neale, BM , Powell, J , Riley, BP , Walters, JT, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Consortium 2 & Purcell, S 2013, 'Genome-wide association analysis identifies 13 new risk loci for schizophrenia', Nature Genetics, vol. 45, no. 10, pp. 1150-1159. https://doi.org/10.1038/ng.2742

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

AU - Ripke, Stephan

AU - O'dushlaine, Colm

AU - Chambert, Kimberly

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AU - K??hler, 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

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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 - Lin, Kuang

AU - Neale, Benjamin M

AU - Powell, John

AU - Riley, Brien P

AU - Walters, James T

AU - Riley, Brien P

AU - Arranz, Maria J

AU - Collier, David

AU - Iyegbe, Conrad

AU - Lewis, Cathryn M

AU - Lin, Kuang

AU - Mata, Ignacio

AU - Murray, Robin M

AU - Powell, John

AU - Van Os, Jim

AU - Walshe, Muriel

AU - Mathew, Christopher G

AU - Plomin, Robert

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Gray, Emma

AU - Weston, Paul

AU - Mathew, Christopher G

AU - Multicenter Genetic Studies of Schizophrenia Consortium

AU - Psychosis Endophenotypes International Consortium

AU - Wellcome Trust Case Consortium 2

AU - Purcell, Shaun

PY - 2013/10

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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

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

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