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

Authors :
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, Pk
Sanchez, N
Stahl, Ea
Williams, S
Wray, Nr
Xia, K
Bettella, F
Borglum, Ad
Bulik Sullivan, Bk
Cormican, P
Craddock, N
Leeuw, De
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, Sarah
Verhage, M
Walters, Jt
Multicenter Genetic Studies of Schizophrenia Consortium
Levinson, Df
Gejman, Pv
Laurent, C
Mowry, Bj
O'Donovan, Mc
Pulver, Ae
Schwab, Sg
Wildenauer, Db
Dudbridge, F
Shi, J
Albus, M
Alexander, M
Campion, D
Cohen, D
Dikeos, D
Duan, J
Eichhammer, P
Godard, S
Hansen, M
Lerer, Fb
Liang, Ky
Maier, W
Mallet, J
Nertney, Da
Nestadt, G
Norton, N
Papadimitriou, Gn
Ribble, R
Sanders, Ar
Silverman, Jm
Walsh, D
Williams, Nm
Wormley, B
Psychosis Endophenotypes International Consortium
Arranz, Mj
Bakker, S
Bender, S
Bramon, E
Collier, D
Crespo Facorro, B
Hall, J
Iyegbe, C
Jablensky, A
Kahn, Rs
Kalaydjieva, L
Lawrie, S
Lewis, Cm
Linszen, Dh
Mata, I
Mcintosh, A
Murray, Rm
Ophoff, Ra
Van, Os
J
Walshe, M
Weisbrod, M
Wiersma, D
Wellcome Trust Case Control Consortium 2
Donnelly, P
Barroso, I
Blackwell, Jm
Brown, Ma
Casas, Jp
Corvin, Ap
Deloukas, P
Duncanson, A
Jankowski, J
Markus, Hs
Mathew, Cg
Palmer, Cn
Plomin, R
Rautanen, A
Sawcer, Sj
Trembath, Rc
Viswanathan, Ac
Wood, Nw
Spencer, Cc
Band, G
Bellenguez, C
Freeman, C
Hellenthal, G
Giannoulatou, E
Pirinen, M
Pearson, Rd
Strange, A
Su, Z
Vukcevic, D
Langford, C
Hunt, Se
Edkins, S
Gwilliam, R
Blackburn, H
Bumpstead, Sj
Dronov, S
Gillman, M
Gray, E
Hammond, N
Jayakumar, A
Mccann, Ot
Liddle, J
Potter, Sc
Ravindrarajah, R
Ricketts, M
Tashakkori Ghanbaria, A
Waller, Mj
Weston, P
Widaa, S
Whittaker, P
Mccarthy, Mi
Stefansson, K
Scolnick, E
Purcell, S
Mccarroll, Sa
Sklar, P
Hultman, Cm
Sullivan, P. F.
Functional Genomics
Molecular and Cellular Neurobiology
AIMMS
Neuroscience Campus Amsterdam - Neurobiology of Mental Health
Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
Adult Psychiatry
Ripke, Stephan
O'Dushlaine, Colm
Chambert, Kimberly
Moran, Jennifer L
Lee, Sang Hong
Sullivan, Patrick F
Multicenter Genetic Studies of Schizophrenia Consortium
Psychosis Endophenotypes International Consortium
Wellcome Trust Case Control Consortium 2
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA deCODE Genet, Reykjavik, Iceland Aarhus Univ Hosp, Risskov, Denmark Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia Statens Serum Inst, DK-2300 Copenhagen, Denmark Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Kings Coll London, Inst Psychiat, London, England Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, DenmarkQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Belgrade, Fac Med, Belgrade, Serbia Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands Kings Coll London, Dept Neurosci, London, England Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA Univ Halle, Dept Psychiat, Halle, Germany Univ Munich, Dept Psychiat, D-80539 Munich, Germany Univ Iceland, Dept Psychiat, Reykjavik, Iceland Landspitali University Hospital Reykjavik, Iceland Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Verona, Sect Psychiat, I-37100 Verona, Italy UCL, Inst Cognit Neurosci, London, England UCL, Mental Hlth Sci Unit, London, England Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA USA
Child and Adolescent Psychiatry / Psychology
Psychiatrie & Neuropsychologie
RS: MHeNs School for Mental Health and Neuroscience
Human genetics
NCA - Brain mechanisms in health and disease
NCA - Neurobiology of mental health
Source :
Nature Genetics, 45(10), 1150-1159. Nature Publishing Group, 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, Sanchez, N, Stahl, E A, Williams, S, Wray, N R, Xia, K, Bettella, F, Borglum, A D, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C A, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, A B, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, T J, Levinson, D F, Gejman, P V, Laurent, C, Mowry, B J, O'Donovan, M C, Pulver, A E, Schwab, S G, Wildenauer, D B, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, F B, Liang, K Y, Maier, W, Mallet, J, Nertney, D A, Nestadt, G, Norton, N, O'Neill, F A, Papadimitriou, G N, Ribble, R, Sanders, A R, Silverman, J M, Wormley, B, Arranz, M J, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, R S, Kalaydjieva, L, Lawrie, S M, Lewis, C M, Linszen, D H, Mata, I, McIntosh, A, Murray, R M, Ophoff, R A, van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Donnely, P, Barasso, I, Blackwell, J M, Brown, M A, Casas, J P, Corvin, A P, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H S, Mathew, C G, Palmer, C N, Plomin, R, Rautanen, A, Sawcer, S J, Trembath, R C, Viswanathan, A C, Wood, N W, Spencer, C C, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R D, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, S E, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, S, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, O T, Liddle, J, Potter, S C, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, M J, Weston, P, Widaa, S, Whittaker, P, Barrroso, I, McCarthy, M I, Spencer, C C, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, S A, Sklar, P, Hultman, C M & Sullivan, P F 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, Nature genetics, 45(10), 1150-1159. Nature Publishing Group, Nature Genetics, 45(10), 1150-U282. Nature Publishing Group, 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, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, A B, Stefansson, H, Steinberg, S, Børglum, A & Multicenter Genetic Studies of Schizophrenia Consortium 2013, ' Genome-wide association analysis identifies 13 new risk loci for schizophrenia ', Nature Genetics . https://doi.org/10.1038/ng.2742, 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, Borglum, A D, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, 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
Publication Year :
2013

Abstract

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. 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. NIMH R01 MH077139 R01 MH095034 Stanley Center for Psychiatric Research Sylvan Herman Foundation Friedman Brain Institute at the Mount Sinai School of Medicine Karolinska Institutet, Karolinska University Hospital Swedish Research Council Swedish County Council Soderstrom Konigska Foundation Netherlands Scientific Organization NWO 645-000-003 info:eu-repo/grantAgreement/EC/FP7/223423 Danish Strategic Research Council H. Lundbeck A/S Faculty of Health Sciences at Aarhus University Lundbeck Foundation Stanley Research Foundation Wellcome Trust 085475/B/08/Z 085475/Z/08/Z

Details

Language :
English
ISSN :
10614036
Database :
OpenAIRE
Journal :
Nature Genetics, 45(10), 1150-1159. Nature Publishing Group, 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, Sanchez, N, Stahl, E A, Williams, S, Wray, N R, Xia, K, Bettella, F, Borglum, A D, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C A, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, A B, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, T J, Levinson, D F, Gejman, P V, Laurent, C, Mowry, B J, O'Donovan, M C, Pulver, A E, Schwab, S G, Wildenauer, D B, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, F B, Liang, K Y, Maier, W, Mallet, J, Nertney, D A, Nestadt, G, Norton, N, O'Neill, F A, Papadimitriou, G N, Ribble, R, Sanders, A R, Silverman, J M, Wormley, B, Arranz, M J, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, R S, Kalaydjieva, L, Lawrie, S M, Lewis, C M, Linszen, D H, Mata, I, McIntosh, A, Murray, R M, Ophoff, R A, van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Donnely, P, Barasso, I, Blackwell, J M, Brown, M A, Casas, J P, Corvin, A P, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H S, Mathew, C G, Palmer, C N, Plomin, R, Rautanen, A, Sawcer, S J, Trembath, R C, Viswanathan, A C, Wood, N W, Spencer, C C, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R D, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, S E, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, S, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, O T, Liddle, J, Potter, S C, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, M J, Weston, P, Widaa, S, Whittaker, P, Barrroso, I, McCarthy, M I, Spencer, C C, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, S A, Sklar, P, Hultman, C M & Sullivan, P F 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, Nature genetics, 45(10), 1150-1159. Nature Publishing Group, Nature Genetics, 45(10), 1150-U282. Nature Publishing Group, 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, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, A B, Stefansson, H, Steinberg, S, Børglum, A & Multicenter Genetic Studies of Schizophrenia Consortium 2013, ' Genome-wide association analysis identifies 13 new risk loci for schizophrenia ', Nature Genetics . https://doi.org/10.1038/ng.2742, 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, Borglum, A D, Bulik-Sullivan, B K, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, M L, Holmans, P, Hougaard, D M, Kendler, K S, Lin, K, Morris, D W, Mors, O, Mortensen, P B, Neale, B M, O'Neill, F A, Owen, M J, Milovancevic, M P, Posthuma, D, Powell, J, Richards, A L, Riley, B P, 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
Accession number :
edsair.doi.dedup.....90ab6ab602c5351fa2e6cf88ebf1ab07
Full Text :
https://doi.org/10.1038/ng.2742