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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Genetics of psychiatric disorders in the GWAS era: an update on schizophrenia
TL;DR: The influence of genetic factors in the development of schizophrenia has been convincingly demonstrated by family, twin, and adoption studies and there is strong indication that in some patients a deletion or insertion of a larger chromosomal region [so-called copy number variation (CNV)] might play a crucial role in pathogenesis.
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Anthony W.S. Chan,Jannet Kocerha +1 more
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The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions.
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TL;DR: This review for the first time systematically presents the evidence for ZNF804A, describing its discovery and likely roles in brain development and schizophrenia pathogenesis, and summarizes this information with a systemic and broad assessment of recent findings.
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Gene-based analyses reveal novel genetic overlap and allelic heterogeneity across five major psychiatric disorders
Huiying Zhao,Dale R. Nyholt +1 more
TL;DR: In this paper, a novel gene-based approach was proposed to extend genetic overlap analysis across the five major disorders from SNP level to gene level using a novel GWA summary results for the five disorders in the Psychiatric Genomics Consortium (PGC).
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Characteristics of the Cation Cotransporter NKCC1 in Human Brain: Alternate Transcripts, Expression in Development, and Potential Relationships to Brain Function and Schizophrenia
Yukitaka Morita,Joseph H. Callicott,Lauren R. Testa,Michelle I. Mighdoll,Dwight Dickinson,Qiang Chen,Qiang Chen,Ran Tao,Ran Tao,Barbara K. Lipska,Bhaskar Kolachana,Amanda J. Law,Amanda J. Law,Tianzhang Ye,Tianzhang Ye,Richard E. Straub,Richard E. Straub,Daniel R. Weinberger,Daniel R. Weinberger,Daniel R. Weinberger,Joel E. Kleinman,Joel E. Kleinman,Thomas M. Hyde,Thomas M. Hyde,Thomas M. Hyde +24 more
TL;DR: Variation in NKCC1 may increase risk for schizophrenia via alterations of mRNA expression at the molecular level and impairment of optimal prefrontal function at the macro or systems level.
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Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
Shaun Purcell,Shaun Purcell,Naomi R. Wray,Jennifer Stone,Jennifer Stone,Peter M. Visscher,Michael Conlon O'Donovan,Patrick F. Sullivan,Pamela Sklar,Pamela Sklar,Douglas M. Ruderfer,Andrew McQuillin,Derek W. Morris,Colm O'Dushlaine,Aiden Corvin,Peter Holmans,Stuart MacGregor,Hugh Gurling,Douglas Blackwood,Nicholas John Craddock,Michael Gill,Christina M. Hultman,Christina M. Hultman,George Kirov,Paul Lichtenstein,Walter J. Muir,Michael John Owen,Carlos N. Pato,Edward M. Scolnick,Edward M. Scolnick,David St Clair,Nigel Williams,Lyudmila Georgieva,Ivan Nikolov,Nadine Norton,Hywel Williams,Draga Toncheva,Vihra Milanova,Emma Flordal Thelander,Patrick Sullivan,Elaine Kenny,Emma M. Quinn,Khalid Choudhury,Susmita Datta,Jonathan Pimm,Srinivasa Thirumalai,Vinay Puri,Robert Krasucki,Jacob Lawrence,Digby Quested,Nicholas Bass,Caroline Crombie,Gillian Fraser,Soh Leh Kuan,Nicholas Walker,Kevin A. McGhee,Ben S. Pickard,P. Malloy,Alan W Maclean,Margaret Van Beck,Michele T. Pato,Helena Medeiros,Frank A. Middleton,Célia Barreto Carvalho,Christopher P. Morley,Ayman H. Fanous,David V. Conti,James A. Knowles,Carlos Ferreira,António Macedo,M. Helena Azevedo,Andrew Kirby,Andrew Kirby,Manuel A. R. Ferreira,Manuel A. R. Ferreira,Mark J. Daly,Mark J. Daly,Kimberly Chambert,Finny G Kuruvilla,Stacey Gabriel,Kristin G. Ardlie,Jennifer L. Moran +81 more
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TL;DR: Evidence is provided that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
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