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 & 31 others 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, Colin N A Palmer, Multicenter Genetic Studies of Schizophrenia Consortium

    Research output: Contribution to journalArticle

    788 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)1150-1159
    Number of pages10
    JournalNature Genetics
    Volume45
    Issue number10
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Genome-Wide Association Study
    Schizophrenia
    Single Nucleotide Polymorphism
    Calcium Signaling
    Bipolar Disorder
    Mental Disorders
    Meta-Analysis
    Public Health
    Genome
    Genes

    Keywords

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

    Cite this

    Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., ... Multicenter Genetic Studies of Schizophrenia Consortium (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
    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 ; Palmer, Colin N A ; Multicenter Genetic Studies of Schizophrenia Consortium. / Genome-wide association analysis identifies 13 new risk loci for schizophrenia. In: Nature Genetics. 2013 ; Vol. 45, No. 10. pp. 1150-1159.
    @article{2cde42e64fca4efeaac563df06dd37c1,
    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 = "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 Palmer, {Colin N A} and {Multicenter Genetic Studies of Schizophrenia Consortium}",
    year = "2013",
    doi = "10.1038/ng.2742",
    language = "English",
    volume = "45",
    pages = "1150--1159",
    journal = "Nature Genetics",
    issn = "1061-4036",
    publisher = "Nature Publishing Group",
    number = "10",

    }

    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, Palmer, CNA & Multicenter Genetic Studies of Schizophrenia Consortium 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

    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; Palmer, Colin N A; Multicenter Genetic Studies of Schizophrenia Consortium.

    In: Nature Genetics, Vol. 45, No. 10, 2013, p. 1150-1159.

    Research output: Contribution to journalArticle

    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 - Palmer, Colin N A

    AU - Multicenter Genetic Studies of Schizophrenia Consortium

    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.

    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

    VL - 45

    SP - 1150

    EP - 1159

    JO - Nature Genetics

    JF - Nature Genetics

    SN - 1061-4036

    IS - 10

    ER -

    Ripke S, O'Dushlaine C, Chambert K, Moran JL, Kähler AK, Akterin S et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics. 2013;45(10):1150-1159. https://doi.org/10.1038/ng.2742