Genome-wide association study identifies five new schizophrenia loci
Stephan Ripke,Alan R. Sanders,Kenneth S. Kendler,Douglas F. Levinson,Pamela Sklar,Pamela Sklar,Peter Holmans,Danyu Lin,Jubao Duan,Roel A. Ophoff,Roel A. Ophoff,Ole A. Andreassen,Edward M. Scolnick,Sven Cichon,David St Clair,Aiden Corvin,Hugh Gurling,Thomas Werge,Dan Rujescu,Douglas Blackwood,Carlos N. Pato,Anil K. Malhotra,Anil K. Malhotra,Shaun Purcell,Frank Dudbridge,Benjamin M. Neale,Lizzy Rossin,Peter M. Visscher,Danielle Posthuma,Douglas M. Ruderfer,Ayman H. Fanous,Ayman H. Fanous,Ayman H. Fanous,Hreinn Stefansson,Stacy Steinberg,Bryan J. Mowry,Vera Golimbet,Marc De Hert,Erik G. Jönsson,István Bitter,Olli Pietiläinen,David A. Collier,Sarah Tosato,Ingrid Agartz,Margot Albus,Madeline Alexander,Richard Amdur,Richard Amdur,Farooq Amin,Farooq Amin,Nicholas Bass,Sarah E. Bergen,Donald W. Black,Anders D. Børglum,Matthew A. Brown,Richard Bruggeman,Nancy G. Buccola,William Byerley,Wiepke Cahn,Rita M. Cantor,Vaughan J. Carr,Stanley V. Catts,Khalid Choudhury,C. Robert Cloninger,Paul Cormican,Nicholas John Craddock,Patrick Danoy,Susmita Datta,Lieuwe de Haan,Ditte Demontis,Dimitris Dikeos,Srdjan Djurovic,Peter Donnelly,Gary Donohoe,L. Duong,Sarah Dwyer,Anders Fink-Jensen,Robert Freedman,Nelson B. Freimer,Marion Friedl,Lyudmila Georgieva,Ina Giegling,Michael Gill,Birte Glenthøj,Stephanie Godard,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Annette M. Hartmann,Frans Henskens,David M. Hougaard,Christina M. Hultman,Andres Ingason,Assen Jablensky,Klaus D. Jakobsen,M. Jay,Gesche Jürgens,René S. Kahn,Matthew C. Keller,Gunter Kenis,Elaine Kenny,Yunjung Kim,George Kirov,H. Konnerth,Bettina Konte,Lydia Krabbendam,Robert Krasucki,Virginia K. Lasseter,Claudine Laurent,Jacob Lawrence,Todd Lencz,Todd Lencz,F. Bernard Lerer,Kung Yee Liang,Paul Lichtenstein,Jeffrey A. Lieberman,Don H. Linszen,Jouko Lönnqvist,Carmel M. Loughland,Alan W Maclean,Brion S. Maher,Wolfgang Maier,J. Mallet,P. Malloy,Manuel Mattheisen,Morten Mattingsdal,Kevin A. McGhee,John J. McGrath,Andrew M. McIntosh,Duncan E. McLean,Andrew McQuillin,Ingrid Melle,Patricia T. Michie,Vihra Milanova,Derek W. Morris,Ole Mors,Preben Bo Mortensen,Valentina Moskvina,Pierandrea Muglia,Inez Myin-Germeys,Deborah A. Nertney,Gerald Nestadt,Jimmi Nielsen,Ivan Nikolov,Merete Nordentoft,Nadine Norton,Markus M. Nöthen,Colm O'Dushlaine,Ann Olincy,Line Olsen,F. Anthony O'Neill,Torben F. Ørntoft,Michael John Owen,Christos Pantelis,George N. Papadimitriou,Michele T. Pato,Leena Peltonen,Leena Peltonen,Hannes Petursson,Ben S. Pickard,Jonathan Pimm,Ann E. Pulver,Vinay Puri,Digby Quested,Emma M. Quinn,Henrik B. Rasmussen,János Réthelyi,R. Ribble,Marcella Rietschel,Marcella Rietschel,Brien P. Riley,Mirella Ruggeri,Ulrich Schall,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Sibylle G. Schwab,Rodney J. Scott,Jianxin Shi,Engilbert Sigurdsson,Jeremy M. Silverman,Jeremy M. Silverman,Chris C. A. Spencer,Kari Stefansson,Amy Strange,Eric Strengman,T. Scott Stroup,Jaana Suvisaari,Lars Terenius,Srinivasa Thirumalai,Johan H. Thygesen,Sally Timm,Draga Toncheva,Edwin J. C. G. van den Oord,Jim van Os,Ruud van Winkel,Ruud van Winkel,Jan H. Veldink,Dermot Walsh,August G. Wang,Durk Wiersma,Dieter B. Wildenauer,Hywel Williams,Nigel Williams,Brandon Wormley,Stan Zammit,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan,Mark J. Daly,Pablo V. Gejman +210 more
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The authors examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects.Abstract:
We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).read more
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Quality control and conduct of genome-wide association meta-analyses
Thomas W. Winkler,Felix R. Day,Damien C. Croteau-Chonka,Andrew R. Wood,Adam E. Locke,Reedik Mägi,Teresa Ferreira,Tove Fall,Mariaelisa Graff,Anne E. Justice,Jian'an Luan,Stefan Gustafsson,Joshua C. Randall,Sailaja Vedantam,Tsegaselassie Workalemahu,Tuomas O. Kilpeläinen,André Scherag,Tõnu Esko,Zoltán Kutalik,Iris M. Heid,Ruth J. F. Loos +20 more
TL;DR: In this article, a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data is presented. But this protocol is not suitable for large consortia such as the GIANT Consortium.
Journal ArticleDOI
Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.
Zhiqiang Li,Jianhua Chen,Hao Yu,Hao Yu,Hao Yu,Lin He,Yifeng Xu,Dai Zhang,Dai Zhang,Dai Zhang,Qizhong Yi,Changgui Li,Xingwang Li,Jiawei Shen,Zhijian Song,Weidong Ji,Meng Wang,Juan Zhou,Boyu Chen,Yahui Liu,Jiqiang Wang,Peng Wang,Ping Yang,Qingzhong Wang,Guoyin Feng,Benxiu Liu,Wensheng Sun,Baojie Li,Guang He,Weidong Li,Chunling Wan,Qi Xu,Wenjin Li,Zujia Wen,Ke Liu,Fang Huang,Jue Ji,Stephan Ripke,Stephan Ripke,Stephan Ripke,Weihua Yue,Weihua Yue,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan,Yongyong Shi +45 more
TL;DR: The genome-wide association study with replication in 36,180 Chinese individuals and transancestry meta-analyses with data from the Psychiatry Genomics Consortium provide novel insight into the genetic architecture and biological etiology of schizophrenia.
Journal ArticleDOI
MicroRNAs in neuronal function and dysfunction.
Heh-In Im,Paul J. Kenny +1 more
TL;DR: Evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction is reviewed.
Journal ArticleDOI
Individual common variants exert weak effects on the risk for autism spectrum disorders.
Richard Anney,Lambertus Klei,Dalila Pinto,Dalila Pinto,Joana Almeida,Elena Bacchelli,Gillian Baird,Nadia Bolshakova,Sven Bölte,Patrick Bolton,Thomas Bourgeron,Thomas Bourgeron,Sean Brennan,Jessica Brian,Jillian P. Casey,Judith Conroy,Catarina Correia,Catarina Correia,Christina Corsello,Emily L. Crawford,Maretha de Jonge,Richard Delorme,Eftichia Duketis,Frederico Duque,Annette Estes,Penny Farrar,Bridget A. Fernandez,Susan E. Folstein,Eric Fombonne,John R. Gilbert,Christopher Gillberg,Joseph T. Glessner,Andrew Green,Jonathan Green,Stephen J. Guter,Elizabeth A. Heron,Richard Holt,Jennifer L. Howe,Gillian Hughes,Vanessa Hus,Roberta Igliozzi,Suma Jacob,Graham Kenny,Cecilia Kim,Alexander Kolevzon,Vlad Kustanovich,Clara Lajonchere,Janine A. Lamb,Miriam Law-Smith,Marion Leboyer,Ann Le Couteur,Bennett L. Leventhal,Bennett L. Leventhal,Xiao-Qing Liu,Frances Lombard,Catherine Lord,Linda Lotspeich,Sabata C. Lund,Tiago R. Magalhaes,Tiago R. Magalhaes,Carine Mantoulan,Christopher J. McDougle,Christopher J. McDougle,Nadine M. Melhem,Alison K. Merikangas,Nancy J. Minshew,Ghazala Mirza,Jeff Munson,Carolyn Noakes,Gudrun Nygren,Katerina Papanikolaou,Alistair T. Pagnamenta,Barbara Parrini,Tara Paton,Andrew Pickles,David J. Posey,Fritz Poustka,Jiannis Ragoussis,Regina Regan,Wendy Roberts,Kathryn Roeder,Bernadette Rogé,Michael Rutter,Sabine Schlitt,Naisha Shah,Val C. Sheffield,Latha Soorya,Inês Sousa,Vera Stoppioni,Nuala Sykes,Raffaella Tancredi,Ann P. Thompson,Susanne Thomson,Ana Tryfon,John Tsiantis,Herman van Engeland,John B. Vincent,Fred R. Volkmar,Jacob A. S. Vorstman,Simon Wallace,Kirsty Wing,Kerstin Wittemeyer,Shawn Wood,Danielle Zurawiecki,Lonnie Zwaigenbaum,Anthony J. Bailey,Agatino Battaglia,Rita M. Cantor,Hilary Coon,Michael L. Cuccaro,Geraldine Dawson,Geraldine Dawson,Sean Ennis,Christine M. Freitag,Daniel H. Geschwind,Jonathan L. Haines,Sabine M. Klauck,William M. McMahon,Elena Maestrini,Judith Miller,Judith Miller,Anthony P. Monaco,Anthony P. Monaco,Stanley F. Nelson,John I. Nurnberger,Guiomar Oliveira,Jeremy R. Parr,Margaret A. Pericak-Vance,Joseph Piven,Gerard D. Schellenberg,Stephen W. Scherer,Astrid M. Vicente,Astrid M. Vicente,Thomas H. Wassink,Ellen M. Wijsman,Catalina Betancur,Catalina Betancur,Catalina Betancur,Joseph D. Buxbaum,Edwin H. Cook,Louise Gallagher,Michael Gill,Joachim Hallmayer,Andrew D. Paterson,James S. Sutcliffe,Peter Szatmari,Veronica J. Vieland,Hakon Hakonarson,Bernie Devlin +148 more
TL;DR: Stage 2 of the Autism Genome Project genome-wide association study is reported, adding 1301 ASD families and bringing the total to 2705 families analysed, and it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Journal ArticleDOI
Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development
Alexander Nord,Matthew J. Blow,Matthew J. Blow,Catia Attanasio,Jennifer A. Akiyama,Amy Holt,Roya Hosseini,Sengthavy Phouanenavong,Ingrid Plajzer-Frick,Malak Shoukry,Veena Afzal,John L.R. Rubenstein,Edward M. Rubin,Edward M. Rubin,Len A. Pennacchio,Len A. Pennacchio,Axel Visel,Axel Visel,Axel Visel +18 more
TL;DR: The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage that underlie processes central to development and disease.
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