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PMID: 23974872 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 45 ·No. 10 ·2013-10-00 ·Pages 1150-9

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, 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, Steinberg S, Suvisaari J, Tosato S, Verhage M, Walters JT, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson DF, Gejman PV, Kendler KS, Laurent C, Mowry BJ, O'Donovan MC, Owen MJ, Pulver AE, Riley BP, Schwab SG, Wildenauer DB, Dudbridge F, Holmans P, 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, O'Neill FA, 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, Lin K, Linszen DH, Mata I, McIntosh A, Murray RM, Ophoff RA, Powell J, Rujescu D, Van Os J, Walshe M, Weisbrod M, Wiersma D, Wellcome Trust Case Control Consortium 2, Donnelly P, Barroso I, Blackwell JM, Bramon E, 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, Donnelly P, 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, Barroso I, Deloukas P, Mathew CG, Blackwell JM, Brown MA, Corvin AP, McCarthy MI, Spencer CC, Bramon E, Corvin AP, O'Donovan MC, Stefansson K, Scolnick E, Purcell S, McCarroll SA, Sklar P, Hultman CM, Sullivan PF

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.

MeSH Terms
Case-Control Studies Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Polymorphism, Single Nucleotide Schizophrenia/genetics Sweden
Authors & Affiliations
190 authors, click to expand affiliations / ORCID
Ripke Stephan
1] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3].
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
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 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
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 C A
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 ORCID
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.2742
Published
2013-10-00
Epub
2013-00-25
Pages
1150-9
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3827979
Subset
IM
Grants
NIMH NIH HHS · R01 MH095034 · United States
Medical Research Council · G0400126 · United Kingdom
Wellcome Trust · 095552 · United Kingdom
NIMH NIH HHS · R01 MH077139 · United States
Wellcome Trust · 085475/B/08/Z · United Kingdom
Medical Research Council · G1100583 · United Kingdom
Medical Research Council · G0600429 · United Kingdom
Medical Research Council · G0901310 · United Kingdom
NIMH NIH HHS · R01 MH083094 · United States
NIMH NIH HHS · U01 MH094421 · United States
Department of Health · PDA/02/06/016 · United Kingdom
Wellcome Trust · 085475/Z/08/Z · United Kingdom
Medical Research Council · G0601635 · United Kingdom
Cancer Research UK · 4584 · United Kingdom
NIMH NIH HHS · K01 MH094406 · United States
Wellcome Trust · 090532 · United Kingdom
Medical Research Council · G0701420 · United Kingdom
Medical Research Council · G0800509 · United Kingdom
Medical Research Council · G1000718 · United Kingdom
External Links
PubMed source DOI: 10.1038/ng.2742 PMC Full Text View journal details
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