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

  • Author(s): 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
  • Lee, Sang Hong
  • Magnusson, Patrik KE
  • 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
  • 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
  • Steinberg, Stacy
  • Suvisaari, Jaana
  • Tosato, Sarah
  • Verhage, Matthijs
  • Walters, James T
  • Multicenter Genetic Studies of Schizophrenia Consortium
  • Levinson, Douglas F
  • Gejman, Pablo V
  • Kendler, Kenneth S
  • Laurent, Claudine
  • Mowry, Bryan J
  • O'Donovan, Michael C
  • Owen, Michael J
  • Pulver, Ann E
  • Riley, Brien P
  • Schwab, Sibylle G
  • Wildenauer, Dieter B
  • Dudbridge, Frank
  • Holmans, Peter
  • 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
  • O'Neill, Francis A
  • Papadimitriou, George N
  • Ribble, Robert
  • Sanders, Alan R
  • Silverman, Jeremy M
  • Walsh, Dermot
  • Williams, Nigel M
  • Wormley, Brandon
  • Psychosis Endophenotypes International Consortium
  • 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
  • Lin, Kuang
  • Linszen, Don H
  • Mata, Ignacio
  • McIntosh, Andrew
  • Murray, Robin M
  • Ophoff, Roel A
  • Powell, John
  • Rujescu, Dan
  • Van Os, Jim
  • Walshe, Muriel
  • Weisbrod, Matthias
  • Wiersma, Durk
  • Wellcome Trust Case Control Consortium 2
  • Donnelly, Peter
  • Barroso, Ines
  • Blackwell, Jenefer M
  • Bramon, Elvira
  • Brown, Matthew A
  • Casas, Juan P
  • Corvin, Aiden P
  • Deloukas, Panos
  • Duncanson, Audrey
  • Jankowski, Janusz
  • Markus, Hugh S
  • Mathew, Christopher G
  • Palmer, Colin NA
  • Plomin, Robert
  • Rautanen, Anna
  • Sawcer, Stephen J
  • Trembath, Richard C
  • Viswanathan, Ananth C
  • Wood, Nicholas W
  • Spencer, Chris CA
  • Band, Gavin
  • Bellenguez, Céline
  • Freeman, Colin
  • Hellenthal, Garrett
  • Giannoulatou, Eleni
  • Pirinen, Matti
  • Pearson, Richard D
  • Strange, Amy
  • Su, Zhan
  • Vukcevic, Damjan
  • Donnelly, Peter
  • 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
  • Mathew, Christopher G
  • Blackwell, Jenefer M
  • Brown, Matthew A
  • Corvin, Aiden P
  • McCarthy, Mark I
  • Spencer, Chris CA
  • Bramon, Elvira
  • Corvin, Aiden P
  • O'Donovan, Michael C
  • Stefansson, Kari
  • Scolnick, Edward
  • Purcell, Shaun
  • McCarroll, Steven A
  • Sklar, Pamela
  • Hultman, Christina M
  • Sullivan, Patrick F
  • et al.

Published Web Location

https://doi.org/10.1038/ng.2742
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.

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