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


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.

SUBMITTER: Ripke S 

PROVIDER: S-EPMC3827979 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Ripke Stephan S   O'Dushlaine Colm C   Chambert Kimberly K   Moran Jennifer L JL   Kähler Anna K AK   Akterin Susanne S   Bergen Sarah E SE   Collins Ann L AL   Crowley James J JJ   Fromer Menachem M   Kim Yunjung Y   Lee Sang Hong SH   Lee Sang Hong SH   Magnusson Patrik K E PK   Sanchez Nick N   Stahl Eli A EA   Williams Stephanie S   Wray Naomi R NR   Xia Kai K   Bettella Francesco F   Borglum Anders D AD   Bulik-Sullivan Brendan K BK   Cormican Paul P   Craddock Nick N   de Leeuw Christiaan C   Durmishi Naser N   Gill Michael M   Golimbet Vera V   Hamshere Marian L ML   Holmans Peter P   Hougaard David M DM   Kendler Kenneth S KS   Lin Kuang K   Morris Derek W DW   Mors Ole O   Mortensen Preben B PB   Neale Benjamin M BM   O'Neill Francis A FA   Owen Michael J MJ   Milovancevic Milica Pejovic MP   Posthuma Danielle D   Powell John J   Richards Alexander L AL   Riley Brien P BP   Ruderfer Douglas D   Rujescu Dan D   Sigurdsson Engilbert E   Silagadze Teimuraz T   Smit August B AB   Stefansson Hreinn H   Steinberg Stacy S   Suvisaari Jaana J   Tosato Sarah S   Verhage Matthijs M   Walters James T JT   Levinson Douglas F DF   Gejman Pablo V PV   Kendler Kenneth S KS   Laurent Claudine C   Mowry Bryan J BJ   O'Donovan Michael C MC   Owen Michael J MJ   Pulver Ann E AE   Riley Brien P BP   Schwab Sibylle G SG   Wildenauer Dieter B DB   Dudbridge Frank F   Holmans Peter P   Shi Jianxin J   Albus Margot M   Alexander Madeline M   Campion Dominique D   Cohen David D   Dikeos Dimitris D   Duan Jubao J   Eichhammer Peter P   Godard Stephanie S   Hansen Mark M   Lerer F Bernard FB   Liang Kung-Yee KY   Maier Wolfgang W   Mallet Jacques J   Nertney Deborah A DA   Nestadt Gerald G   Norton Nadine N   O'Neill Francis A FA   Papadimitriou George N GN   Ribble Robert R   Sanders Alan R AR   Silverman Jeremy M JM   Walsh Dermot D   Williams Nigel M NM   Wormley Brandon B   Arranz Maria J MJ   Bakker Steven S   Bender Stephan S   Bramon Elvira E   Collier David D   Crespo-Facorro Benedicto B   Hall Jeremy J   Iyegbe Conrad C   Jablensky Assen A   Kahn Rene S RS   Kalaydjieva Luba L   Lawrie Stephen S   Lewis Cathryn M CM   Lin Kuang K   Linszen Don H DH   Mata Ignacio I   McIntosh Andrew A   Murray Robin M RM   Ophoff Roel A RA   Powell John J   Rujescu Dan D   Van Os Jim J   Walshe Muriel M   Weisbrod Matthias M   Wiersma Durk D   Donnelly Peter P   Barroso Ines I   Blackwell Jenefer M JM   Bramon Elvira E   Brown Matthew A MA   Casas Juan P JP   Corvin Aiden P AP   Deloukas Panos P   Duncanson Audrey A   Jankowski Janusz J   Markus Hugh S HS   Mathew Christopher G CG   Palmer Colin N A CN   Plomin Robert R   Rautanen Anna A   Sawcer Stephen J SJ   Trembath Richard C RC   Viswanathan Ananth C AC   Wood Nicholas W NW   Spencer Chris C A CC   Band Gavin G   Bellenguez Céline C   Freeman Colin C   Hellenthal Garrett G   Giannoulatou Eleni E   Pirinen Matti M   Pearson Richard D RD   Strange Amy A   Su Zhan Z   Vukcevic Damjan D   Donnelly Peter P   Langford Cordelia C   Hunt Sarah E SE   Edkins Sarah S   Gwilliam Rhian R   Blackburn Hannah H   Bumpstead Suzannah J SJ   Dronov Serge S   Gillman Matthew M   Gray Emma E   Hammond Naomi N   Jayakumar Alagurevathi A   McCann Owen T OT   Liddle Jennifer J   Potter Simon C SC   Ravindrarajah Radhi R   Ricketts Michelle M   Tashakkori-Ghanbaria Avazeh A   Waller Matthew J MJ   Weston Paul P   Widaa Sara S   Whittaker Pamela P   Barroso Ines I   Deloukas Panos P   Mathew Christopher G CG   Blackwell Jenefer M JM   Brown Matthew A MA   Corvin Aiden P AP   McCarthy Mark I MI   Spencer Chris C A CC   Bramon Elvira E   Corvin Aiden P AP   O'Donovan Michael C MC   Stefansson Kari K   Scolnick Edward E   Purcell Shaun S   McCarroll Steven A SA   Sklar Pamela P   Hultman Christina M CM   Sullivan Patrick F PF  

Nature genetics 20130825 10


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 t  ...[more]

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