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

S Ripke; C O'Dushlaine; K Chambert; JL Moran; AK Kahler; S Akterin; SE Bergen; AL Collins; JJ Crowley; M Fromer; Y. Kim; SH Lee; PKE Magnusson; N Sanchez; EA Stahl; S Williams; NR Wray; K Xia; F Bettella; AD Borglum; BK Bulik-Sullivan; P Cormican; N Craddock; C de Leeuw; N Durmishi; M Gill; V Golimbet; ML Hamshere; P Holmans; DM Hougaard; KS Kendler; K Lin; DW Morris; O Mors; PB Mortensen; BM Neale; FA O'Neill; MJ Owen; MP Milovancevic; Daniëlle Posthuma; J Powell; AL Richards; BP Riley; D Ruderfer; D Rujescu; E Sigurdsson; T Silagadze; AB Smit; H Stefansson; S Steinberg; J Suvisaari; S Tosato; M Verhage; JT Walters; E Bramon; AP Corvin; MC O'Donovan; K Stefansson; E Scolnick; S Purcell; SA McCarroll; P Sklar; CM Hultman; PF Sullivan

doi:10.1038/ng.2742

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

S Ripke, C O'Dushlaine, K Chambert, JL Moran, AK Kahler, S Akterin, SE Bergen, AL Collins, JJ Crowley, M Fromer, Y. Kim, SH Lee, PKE Magnusson, N Sanchez, EA Stahl, S Williams, NR Wray, K Xia, F Bettella, AD BorglumBK Bulik-Sullivan, P Cormican, N Craddock, C de Leeuw, N Durmishi, M Gill, V Golimbet, ML Hamshere, P Holmans, DM Hougaard, KS Kendler, K Lin, DW Morris, O Mors, PB Mortensen, BM Neale, FA O'Neill, MJ Owen, MP Milovancevic, Daniëlle Posthuma, J Powell, AL Richards, BP Riley, D Ruderfer, D Rujescu, E Sigurdsson, T Silagadze, AB Smit, H Stefansson, S Steinberg, J Suvisaari, S Tosato, M Verhage, JT Walters, E Bramon, AP Corvin, MC O'Donovan, K Stefansson, E Scolnick, S Purcell, SA McCarroll, P Sklar, CM Hultman, PF Sullivan

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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	Undefined/Unknown
Pages (from-to)	1150-U282
Journal	Nature Genetics
Volume	45
Issue number	10
DOIs	https://doi.org/10.1038/ng.2742
Publication status	Published - 2013

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10.1038/ng.2742

http://hdl.handle.net/1765/55967

Cite this

Ripke, S., O'Dushlaine, C., Chambert, K., Moran, JL., Kahler, 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., ... Sullivan, PF. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150-U282. 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.",

author = "S Ripke and C O'Dushlaine and K Chambert and JL Moran and AK Kahler and S Akterin and SE Bergen and AL Collins and JJ Crowley and M Fromer and Y. Kim and SH Lee and PKE Magnusson and N Sanchez and EA Stahl and S Williams and NR Wray and K Xia and F Bettella and AD Borglum and BK Bulik-Sullivan and P Cormican and N Craddock and \{de Leeuw\}, C and N Durmishi and M Gill and V Golimbet and ML Hamshere and P Holmans and DM Hougaard and KS Kendler and K Lin and DW Morris and O Mors and PB Mortensen and BM Neale and FA O'Neill and MJ Owen and MP Milovancevic and Dani{\"e}lle Posthuma and J Powell and AL Richards and BP Riley and D Ruderfer and D Rujescu and E Sigurdsson and T Silagadze and AB Smit and H Stefansson and S Steinberg and J Suvisaari and S Tosato and M Verhage and JT Walters and E Bramon and AP Corvin and MC O'Donovan and K Stefansson and E Scolnick and S Purcell and SA McCarroll and P Sklar and CM Hultman and PF Sullivan",

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Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kahler, 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, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Bramon, E, Corvin, AP, O'Donovan, MC, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM & Sullivan, PF 2013, 'Genome-wide association analysis identifies 13 new risk loci for schizophrenia', Nature Genetics, vol. 45, no. 10, pp. 1150-U282. https://doi.org/10.1038/ng.2742

TY - JOUR

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

AU - Ripke, S

AU - O'Dushlaine, C

AU - Chambert, K

AU - Moran, JL

AU - Kahler, AK

AU - Akterin, S

AU - Bergen, SE

AU - Collins, AL

AU - Crowley, JJ

AU - Fromer, M

AU - Kim, Y.

AU - Lee, SH

AU - Magnusson, PKE

AU - Sanchez, N

AU - Stahl, EA

AU - Williams, S

AU - Wray, NR

AU - Xia, K

AU - Bettella, F

AU - Borglum, AD

AU - Bulik-Sullivan, BK

AU - Cormican, P

AU - Craddock, N

AU - de Leeuw, C

AU - Durmishi, N

AU - Gill, M

AU - Golimbet, V

AU - Hamshere, ML

AU - Holmans, P

AU - Hougaard, DM

AU - Kendler, KS

AU - Lin, K

AU - Morris, DW

AU - Mors, O

AU - Mortensen, PB

AU - Neale, BM

AU - O'Neill, FA

AU - Owen, MJ

AU - Milovancevic, MP

AU - Posthuma, Daniëlle

AU - Powell, J

AU - Richards, AL

AU - Riley, BP

AU - Ruderfer, D

AU - Rujescu, D

AU - Sigurdsson, E

AU - Silagadze, T

AU - Smit, AB

AU - Stefansson, H

AU - Steinberg, S

AU - Suvisaari, J

AU - Tosato, S

AU - Verhage, M

AU - Walters, JT

AU - Bramon, E

AU - Corvin, AP

AU - O'Donovan, MC

AU - Stefansson, K

AU - Scolnick, E

AU - Purcell, S

AU - McCarroll, SA

AU - Sklar, P

AU - Hultman, CM

AU - Sullivan, PF

PY - 2013

Y1 - 2013

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.

U2 - 10.1038/ng.2742

DO - 10.1038/ng.2742

M3 - Article

C2 - 23974872

SN - 1061-4036

VL - 45

SP - 1150-U282

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -