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 (US) |
|---|---|
| Pages (from-to) | 1150-1159 |
| Number of pages | 10 |
| Journal | Nature genetics |
| Volume | 45 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2013 |
ASJC Scopus subject areas
- Genetics
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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; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B.; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T.; Levinson, Douglas F.; Gejman, Pablo V.; Laurent, Claudine; Mowry, Bryan J.; O'Donovan, Michael C.; Pulver, Ann E.; Schwab, Sibylle G.; Wildenauer, Dieter B.; Dudbridge, Frank; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F. Bernard; Liang, Kung Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A.; Nestadt, Gerald; Norton, Nadine; Papadimitriou, George N.; Ribble, Robert; Sanders, Alan R.; Silverman, Jeremy M.; Walsh, Dermot; Williams, Nigel M.; Wormley, Brandon; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M.; Linszen, Don H.; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M.; Ophoff, Roel A.; Rujescu, Dan; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden P.; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D.; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J.; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; McCarthy, Mark I.; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A.; Sklar, Pamela; Hultman, Christina M.; Sullivan, Patrick F.
In: Nature genetics, Vol. 45, No. 10, 10.2013, 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 - Sigurdsson, Engilbert
AU - Silagadze, Teimuraz
AU - Smit, August B.
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Suvisaari, Jaana
AU - Tosato, Sarah
AU - Verhage, Matthijs
AU - Walters, James T.
AU - Levinson, Douglas F.
AU - Gejman, Pablo V.
AU - Laurent, Claudine
AU - Mowry, Bryan J.
AU - O'Donovan, Michael C.
AU - Pulver, Ann E.
AU - Schwab, Sibylle G.
AU - Wildenauer, Dieter B.
AU - Dudbridge, Frank
AU - Shi, Jianxin
AU - Albus, Margot
AU - Alexander, Madeline
AU - Campion, Dominique
AU - Cohen, David
AU - Dikeos, Dimitris
AU - Duan, Jubao
AU - Eichhammer, Peter
AU - Godard, Stephanie
AU - Hansen, Mark
AU - Lerer, F. Bernard
AU - Liang, Kung Yee
AU - Maier, Wolfgang
AU - Mallet, Jacques
AU - Nertney, Deborah A.
AU - Nestadt, Gerald
AU - Norton, Nadine
AU - Papadimitriou, George N.
AU - Ribble, Robert
AU - Sanders, Alan R.
AU - Silverman, Jeremy M.
AU - Walsh, Dermot
AU - Williams, Nigel M.
AU - Wormley, Brandon
AU - Arranz, Maria J.
AU - Bakker, Steven
AU - Bender, Stephan
AU - Bramon, Elvira
AU - Collier, David
AU - Crespo-Facorro, Benedicto
AU - Hall, Jeremy
AU - Iyegbe, Conrad
AU - Jablensky, Assen
AU - Kahn, Rene S.
AU - Kalaydjieva, Luba
AU - Lawrie, Stephen
AU - Lewis, Cathryn M.
AU - Linszen, Don H.
AU - Mata, Ignacio
AU - McIntosh, Andrew
AU - Murray, Robin M.
AU - Ophoff, Roel A.
AU - Rujescu, Dan
AU - Van Os, Jim
AU - Walshe, Muriel
AU - Weisbrod, Matthias
AU - Wiersma, Durk
AU - Donnelly, Peter
AU - Blackwell, Jenefer M.
AU - Brown, Matthew A.
AU - Casas, Juan P.
AU - Corvin, Aiden P.
AU - Duncanson, Audrey
AU - Jankowski, Janusz
AU - Markus, Hugh S.
AU - Mathew, Christopher G.
AU - Palmer, Colin N.A.
AU - Plomin, Robert
AU - Rautanen, Anna
AU - Sawcer, Stephen J.
AU - Trembath, Richard C.
AU - Viswanathan, Ananth C.
AU - Wood, Nicholas W.
AU - Spencer, Chris C.A.
AU - Band, Gavin
AU - Bellenguez, Céline
AU - Freeman, Colin
AU - Hellenthal, Garrett
AU - Giannoulatou, Eleni
AU - Pirinen, Matti
AU - Pearson, Richard D.
AU - Strange, Amy
AU - Su, Zhan
AU - Vukcevic, Damjan
AU - Langford, Cordelia
AU - Hunt, Sarah E.
AU - Edkins, Sarah
AU - Gwilliam, Rhian
AU - Blackburn, Hannah
AU - Bumpstead, Suzannah J.
AU - Dronov, Serge
AU - Gillman, Matthew
AU - Gray, Emma
AU - Hammond, Naomi
AU - Jayakumar, Alagurevathi
AU - McCann, Owen T.
AU - Liddle, Jennifer
AU - Potter, Simon C.
AU - Ravindrarajah, Radhi
AU - Ricketts, Michelle
AU - Tashakkori-Ghanbaria, Avazeh
AU - Waller, Matthew J.
AU - Weston, Paul
AU - Widaa, Sara
AU - Whittaker, Pamela
AU - Barroso, Ines
AU - Deloukas, Panos
AU - McCarthy, Mark I.
AU - Stefansson, Kari
AU - Scolnick, Edward
AU - Purcell, Shaun
AU - McCarroll, Steven A.
AU - Sklar, Pamela
AU - Hultman, Christina M.
AU - Sullivan, Patrick F.
N1 - Funding Information: We are deeply grateful for the participation of all subjects contributing to this research and to the collection team that worked to recruit them: E. Flordal-Thelander, A.-B. Holmgren, M. Hallin, M. Lundin, A.-K. Sundberg, C. Pettersson, R. Satgunanthan-Dawoud, S. Hassellund, M. Rådstrom, B. Ohlander, L. Nyrén and I. Kizling. Funding support was provided by the NIMH (R01 MH077139 to P.F.S. and R01 MH095034 to P.S.), the Stanley Center for Psychiatric Research, the Sylvan Herman Foundation, the Friedman Brain Institute at the Mount Sinai School of Medicine, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the Söderström Königska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). SGENE was supported by European Union grant HEALTH-F2-2009-223423 (project PsychCNVs). The study of the Aarhus sample was supported by grants from the Danish Strategic Research Council, H. Lundbeck A/S, the Faculty of Health Sciences at Aarhus University, the Lundbeck Foundation and the Stanley Research Foundation. The Wellcome Trust Case Control Consortium 2 project collection was funded by the Wellcome Trust (085475/B/08/Z and 085475/Z/08/Z). The funders had no role in study design, execution or analysis or in manuscript preparation.
PY - 2013/10
Y1 - 2013/10
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.
UR - http://www.scopus.com/inward/record.url?scp=84885020424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885020424&partnerID=8YFLogxK
U2 - 10.1038/ng.2742
DO - 10.1038/ng.2742
M3 - Article
C2 - 23974872
AN - SCOPUS:84885020424
VL - 45
SP - 1150
EP - 1159
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 10
ER -