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Journal Articles Nature Genetics Year : 2017

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Christian R Marshall , Daniel P Howrigan , Daniele Merico , Bhooma Thiruvahindrapuram , Wenting Wu , Douglas S Greer , Danny Antaki , Aniket Shetty , Peter A Holmans , Dalila Pinto , Madhusudan Gujral , William M Brandler , Dheeraj Malhotra , Zhouzhi Wang , Karin V Fuentes Fajarado , Michelle S Maile , Stephan Ripke , Ingrid Agartz , Margot Albus , Madeline Alexander , Farooq Amin , Joshua Atkins , Silviu A Bacanu , Richard A Belliveau , Sarah E Bergen , Marcelo Bertalan , Elizabeth Bevilacqua , Tim B Bigdeli , Donald W Black , Richard Bruggeman , Nancy G Buccola , Randy L Buckner , Brendan Bulik-Sullivan , William Byerley , Wiepke Cahn , Guiqing Cai , Murray J Cairns , Dominique Campion , Rita M Cantor , Vaughan J Carr , Noa Carrera , Stanley V Catts , Kimberley D Chambert , Wei Cheng , C. Robert Cloninger , David Cohen (1) , Paul Cormican , Nick Craddock , Benedicto Crespo-Facorro , James J Crowley , David Curtis , Michael Davidson , Kenneth L Davis , Franziska Degenhardt , Jurgen del Favero , Lynn E Delisi , Dimitris Dikeos , Timothy Dinan , Srdjan Djurovic , Gary Donohoe , Elodie Drapeau , Jubao Duan , Frank Dudbridge , Peter Eichhammer , Johan Eriksson , Valentina Escott-Price , Laurent Essioux , Ayman H Fanous , Kai-How Farh , Martilias S Farrell , Josef Frank , Lude Franke , Robert Freedman , Nelson B Freimer , Joseph I Friedman , Andreas J Forstner , Menachem Fromer , Giulio Genovese , Lyudmila Georgieva , Elliot S Gershon , Ina Giegling , Paola Giusti-Rodríguez , Stephanie Godard (2, 3) , Jacqueline I Goldstein , Jacob Gratten , Lieuwe de Haan , Marian L Hamshere , Mark Hansen , Thomas Hansen , Vahram Haroutunian , Annette M Hartmann , Frans A Henskens , Stefan Herms , Joel N Hirschhorn , Per Hoffmann , Andrea Hofman , Hailiang Huang , Masashi Ikeda , Inge Joa , Anna K Kähler , René S Kahn , Luba Kalaydjieva , Juha Karjalainen , David Kavanagh , Matthew C Keller , Brian J Kelly , James L Kennedy , Yunjung Kim , James A Knowles , Bettina Konte , Claudine Laurent (3) , Phil Lee , S. Hong Lee , Sophie E Legge , Bernard Lerer , Deborah L Levy , Kung-Yee Liang , Jeffrey Lieberman , Jouko Lönnqvist , Carmel M Loughland , Patrik K.E. Magnusson , Brion S Maher , Wolfgang Maier , Jacques Mallet (3, 4, 5) , Manuel Mattheisen , Morten Mattingsdal , Robert W Mccarley , Colm McDonald , Andrew M Mcintosh , Sandra Meier , Carin J Meijer , Ingrid Melle , Raquelle I Mesholam-Gately , Andres Metspalu , Patricia T Michie , Lili Milani , Vihra Milanova , Younes Mokrab , Derek W Morris , Bertram Müller-Myhsok , Kieran C Murphy , Robin M Murray , Inez Myin-Germeys , Igor Nenadic , Deborah A Nertney , Gerald Nestadt , Kristin K Nicodemus , Laura Nisenbaum , Annelie Nordin , Eadbhard O’callaghan , Colm O’dushlaine , Sang-Yun Oh , Ann Olincy , Line Olsen , F. Anthony O’neill , Jim van Os , Christos Pantelis , George N Papadimitriou , Elena Parkhomenko , Michele T Pato , Tiina Paunio , Diana O Perkins , Tune H Pers , Olli Pietiläinen , Jonathan Pimm , Andrew J Pocklington , John Powell , Alkes Price , Ann E Pulver , Shaun M Purcell , Digby Quested , Henrik B Rasmussen , Abraham Reichenberg , Mark A Reimers , Alexander L Richards , Joshua L Roffman , Panos Roussos , Douglas M Ruderfer , Veikko Salomaa , Alan R Sanders , Adam Savitz , Ulrich Schall , Thomas G Schulze , Sibylle G Schwab , Edward M Scolnick , Rodney J Scott , Larry J Seidman , Jianxin Shi , Jeremy M Silverman , Jordan W Smoller , Erik Söderman , Chris C.A. Spencer , Eli A Stahl , Eric Strengman , Jana Strohmaier , T. Scott Stroup , Jaana Suvisaari , Dragan M Svrakic , Jin P Szatkiewicz , Srinivas Thirumalai , Paul A Tooney , Juha Veijola , Peter M Visscher , John Waddington , Dermot Walsh , Bradley T Webb , Mark Weiser , Dieter B Wildenauer , Nigel M Williams , Stephanie Williams , Stephanie H Witt , Aaron R Wolen , Brandon K Wormley , Naomi R Wray , Jing Qin Wu , Clement C Zai , Rolf Adolfsson , Ole A Andreassen , Douglas H.R. Blackwood , Elvira Bramon , Joseph D Buxbaum , Sven Cichon , David A Collier , Aiden Corvin , Mark J Daly , Ariel Darvasi , Enrico Domenici , Tõnu Esko , Pablo V Gejman , Michael Gill , Hugh Gurling , Christina M Hultman , Nakao Iwata , Assen V Jablensky , Erik G Jönsson , Kenneth S Kendler , George Kirov , Jo Knight , Douglas F Levinson , Qingqin S Li , Steven A Mccarroll , Andrew Mcquillin , Jennifer L Moran , Bryan J Mowry , Markus M Nöthen , Roel A Ophoff , Michael J Owen , Aarno Palotie , Carlos N Pato , Tracey L Petryshen , Danielle Posthuma , Marcella Rietschel , Brien P Riley , Dan Rujescu , Pamela Sklar , David St. Clair , James T.R. Walters , Thomas Werge , Patrick F Sullivan , Michael O’donovan , Stephen W Scherer , Benjamin M Neale , Jonathan Sebat , C Robert Cloninger , S Hong Lee , Patrik K E Magnusson , Eadbhard O'Callaghan , Colm O'Dushlaine , F Anthony O'Neill , Chris C A Spencer , T Scott Stroup , Douglas H R Blackwood , David St Clair , James T R Walters , Michael C O'Donovan
Christian R Marshall
  • Function : Author
Daniel P Howrigan
  • Function : Author
Daniele Merico
  • Function : Author
Bhooma Thiruvahindrapuram
  • Function : Author
Wenting Wu
  • Function : Author
Douglas S Greer
  • Function : Author
Danny Antaki
  • Function : Author
Aniket Shetty
  • Function : Author
Peter A Holmans
  • Function : Author
Dalila Pinto
Madhusudan Gujral
  • Function : Author
William M Brandler
  • Function : Author
Dheeraj Malhotra
  • Function : Author
Zhouzhi Wang
  • Function : Author
Karin V Fuentes Fajarado
  • Function : Author
Michelle S Maile
  • Function : Author
Stephan Ripke
Ingrid Agartz
  • Function : Author
Margot Albus
  • Function : Author
Madeline Alexander
  • Function : Author
Farooq Amin
  • Function : Author
Joshua Atkins
  • Function : Author
Silviu A Bacanu
  • Function : Author
Richard A Belliveau
  • Function : Author
Sarah E Bergen
  • Function : Author
Marcelo Bertalan
  • Function : Author
Elizabeth Bevilacqua
  • Function : Author
Tim B Bigdeli
  • Function : Author
Donald W Black
  • Function : Author
Richard Bruggeman
  • Function : Author
Nancy G Buccola
  • Function : Author
Randy L Buckner
  • Function : Author
Brendan Bulik-Sullivan
  • Function : Author
William Byerley
  • Function : Author
Wiepke Cahn
  • Function : Author
Guiqing Cai
  • Function : Author
Murray J Cairns
  • Function : Author
Dominique Campion
  • Function : Author
Rita M Cantor
  • Function : Author
Vaughan J Carr
  • Function : Author
Noa Carrera
  • Function : Author
Stanley V Catts
  • Function : Author
Kimberley D Chambert
  • Function : Author
Wei Cheng
  • Function : Author
C. Robert Cloninger
  • Function : Author
Paul Cormican
  • Function : Author
Nick Craddock
  • Function : Author
Benedicto Crespo-Facorro
  • Function : Author
James J Crowley
  • Function : Author
David Curtis
  • Function : Author
Michael Davidson
  • Function : Author
Kenneth L Davis
  • Function : Author
Franziska Degenhardt
  • Function : Author
Jurgen del Favero
  • Function : Author
Lynn E Delisi
  • Function : Author
Dimitris Dikeos
  • Function : Author
Timothy Dinan
  • Function : Author
Srdjan Djurovic
  • Function : Author
Gary Donohoe
  • Function : Author
Elodie Drapeau
  • Function : Author
Jubao Duan
  • Function : Author
Frank Dudbridge
  • Function : Author
Peter Eichhammer
  • Function : Author
Johan Eriksson
  • Function : Author
Valentina Escott-Price
  • Function : Author
Laurent Essioux
  • Function : Author
Ayman H Fanous
  • Function : Author
Kai-How Farh
  • Function : Author
Martilias S Farrell
Josef Frank
Lude Franke
Robert Freedman
  • Function : Author
Nelson B Freimer
Joseph I Friedman
  • Function : Author
Andreas J Forstner
  • Function : Author
Menachem Fromer
  • Function : Author
Giulio Genovese
  • Function : Author
Lyudmila Georgieva
  • Function : Author
Elliot S Gershon
  • Function : Author
Ina Giegling
  • Function : Author
Paola Giusti-Rodríguez
  • Function : Author
Jacqueline I Goldstein
  • Function : Author
Jacob Gratten
  • Function : Author
Lieuwe de Haan
  • Function : Author
Marian L Hamshere
  • Function : Author
Mark Hansen
  • Function : Author
Thomas Hansen
Vahram Haroutunian
  • Function : Author
Annette M Hartmann
  • Function : Author
Frans A Henskens
  • Function : Author
Stefan Herms
  • Function : Author
Joel N Hirschhorn
  • Function : Author
Per Hoffmann
  • Function : Author
Andrea Hofman
  • Function : Author
Hailiang Huang
Masashi Ikeda
  • Function : Author
Inge Joa
  • Function : Author
Anna K Kähler
  • Function : Author
René S Kahn
  • Function : Author
Luba Kalaydjieva
  • Function : Author
Juha Karjalainen
  • Function : Author
David Kavanagh
  • Function : Author
Matthew C Keller
  • Function : Author
Brian J Kelly
  • Function : Author
James L Kennedy
  • Function : Author
Yunjung Kim
  • Function : Author
James A Knowles
Bettina Konte
Phil Lee
  • Function : Author
S. Hong Lee
  • Function : Author
Sophie E Legge
  • Function : Author
Bernard Lerer
  • Function : Author
Deborah L Levy
  • Function : Author
Kung-Yee Liang
  • Function : Author
Jeffrey Lieberman
  • Function : Author
Jouko Lönnqvist
  • Function : Author
Carmel M Loughland
  • Function : Author
Patrik K.E. Magnusson
  • Function : Author
Brion S Maher
  • Function : Author
Wolfgang Maier
  • Function : Author
Manuel Mattheisen
Morten Mattingsdal
  • Function : Author
Robert W Mccarley
  • Function : Author
Colm McDonald
  • Function : Author
Andrew M Mcintosh
Sandra Meier
  • Function : Author
Carin J Meijer
  • Function : Author
Ingrid Melle
  • Function : Author
Raquelle I Mesholam-Gately
  • Function : Author
Andres Metspalu
  • Function : Author
Patricia T Michie
  • Function : Author
Lili Milani
Vihra Milanova
  • Function : Author
Younes Mokrab
  • Function : Author
Derek W Morris
  • Function : Author
Bertram Müller-Myhsok
  • Function : Author
Kieran C Murphy
  • Function : Author
Robin M Murray
  • Function : Author
Inez Myin-Germeys
  • Function : Author
Igor Nenadic
  • Function : Author
Deborah A Nertney
  • Function : Author
Gerald Nestadt
  • Function : Author
Kristin K Nicodemus
  • Function : Author
Laura Nisenbaum
  • Function : Author
Annelie Nordin
  • Function : Author
Eadbhard O’callaghan
  • Function : Author
Colm O’dushlaine
  • Function : Author
Sang-Yun Oh
  • Function : Author
Ann Olincy
  • Function : Author
Line Olsen
  • Function : Author
F. Anthony O’neill
  • Function : Author
Jim van Os
  • Function : Author
Christos Pantelis
  • Function : Author
George N Papadimitriou
  • Function : Author
Elena Parkhomenko
  • Function : Author
Michele T Pato
  • Function : Author
Tiina Paunio
  • Function : Author
Diana O Perkins
  • Function : Author
Tune H Pers
  • Function : Author
Olli Pietiläinen
  • Function : Author
Jonathan Pimm
  • Function : Author
Andrew J Pocklington
  • Function : Author
John Powell
  • Function : Author
Alkes Price
  • Function : Author
Ann E Pulver
  • Function : Author
Shaun M Purcell
  • Function : Author
Digby Quested
  • Function : Author
Henrik B Rasmussen
  • Function : Author
Abraham Reichenberg
  • Function : Author
Mark A Reimers
  • Function : Author
Alexander L Richards
  • Function : Author
Joshua L Roffman
  • Function : Author
Panos Roussos
  • Function : Author
Douglas M Ruderfer
  • Function : Author
Veikko Salomaa
  • Function : Author
Alan R Sanders
  • Function : Author
Adam Savitz
  • Function : Author
Ulrich Schall
  • Function : Author
Thomas G Schulze
  • Function : Author
Sibylle G Schwab
  • Function : Author
Edward M Scolnick
  • Function : Author
Rodney J Scott
  • Function : Author
Larry J Seidman
  • Function : Author
Jianxin Shi
  • Function : Author
Jeremy M Silverman
  • Function : Author
Jordan W Smoller
  • Function : Author
Erik Söderman
  • Function : Author
Chris C.A. Spencer
  • Function : Author
Eli A Stahl
  • Function : Author
Eric Strengman
  • Function : Author
Jana Strohmaier
  • Function : Author
T. Scott Stroup
  • Function : Author
Jaana Suvisaari
  • Function : Author
Dragan M Svrakic
  • Function : Author
Jin P Szatkiewicz
  • Function : Author
Srinivas Thirumalai
  • Function : Author
Paul A Tooney
  • Function : Author
Juha Veijola
  • Function : Author
Peter M Visscher
  • Function : Author
John Waddington
  • Function : Author
Dermot Walsh
  • Function : Author
Bradley T Webb
  • Function : Author
Mark Weiser
  • Function : Author
Dieter B Wildenauer
  • Function : Author
Nigel M Williams
  • Function : Author
Stephanie Williams
  • Function : Author
Stephanie H Witt
  • Function : Author
Aaron R Wolen
  • Function : Author
Brandon K Wormley
  • Function : Author
Naomi R Wray
  • Function : Author
Jing Qin Wu
  • Function : Author
Clement C Zai
  • Function : Author
Rolf Adolfsson
  • Function : Author
Ole A Andreassen
  • Function : Author
Douglas H.R. Blackwood
  • Function : Author
Elvira Bramon
  • Function : Author
Joseph D Buxbaum
  • Function : Author
Sven Cichon
  • Function : Author
David A Collier
  • Function : Author
Aiden Corvin
  • Function : Author
Mark J Daly
  • Function : Author
Ariel Darvasi
  • Function : Author
Enrico Domenici
  • Function : Author
Tõnu Esko
  • Function : Author
Pablo V Gejman
  • Function : Author
Michael Gill
  • Function : Author
Hugh Gurling
  • Function : Author
Christina M Hultman
  • Function : Author
Nakao Iwata
  • Function : Author
Assen V Jablensky
  • Function : Author
Erik G Jönsson
  • Function : Author
Kenneth S Kendler
  • Function : Author
George Kirov
  • Function : Author
Jo Knight
  • Function : Author
Douglas F Levinson
  • Function : Author
Qingqin S Li
  • Function : Author
Steven A Mccarroll
  • Function : Author
Andrew Mcquillin
  • Function : Author
Jennifer L Moran
  • Function : Author
Bryan J Mowry
  • Function : Author
Markus M Nöthen
  • Function : Author
Roel A Ophoff
  • Function : Author
Michael J Owen
  • Function : Author
Aarno Palotie
  • Function : Author
Carlos N Pato
  • Function : Author
Tracey L Petryshen
  • Function : Author
Danielle Posthuma
  • Function : Author
Marcella Rietschel
  • Function : Author
Brien P Riley
  • Function : Author
Dan Rujescu
  • Function : Author
Pamela Sklar
  • Function : Author
David St. Clair
  • Function : Author
James T.R. Walters
  • Function : Author
Thomas Werge
  • Function : Author
Patrick F Sullivan
  • Function : Author
Michael O’donovan
  • Function : Author
Stephen W Scherer
  • Function : Author
Benjamin M Neale
  • Function : Author
Jonathan Sebat
C Robert Cloninger
S Hong Lee
  • Function : Author
Patrik K E Magnusson
  • Function : Author
Eadbhard O'Callaghan
  • Function : Author
Colm O'Dushlaine
  • Function : Author
F Anthony O'Neill
  • Function : Author
Chris C A Spencer
  • Function : Author
T Scott Stroup
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Douglas H R Blackwood
  • Function : Author
David St Clair
  • Function : Author
James T R Walters
  • Function : Author
Michael C O'Donovan
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Abstract

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
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Dates and versions

hal-04589228 , version 1 (27-05-2024)

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Christian R Marshall, Daniel P Howrigan, Daniele Merico, Bhooma Thiruvahindrapuram, Wenting Wu, et al.. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nature Genetics, 2017, 49 (1), pp.27 - 35. ⟨10.1038/ng.3725⟩. ⟨hal-04589228⟩
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