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 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
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
}
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.
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 -