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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TLDR
The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.Abstract:
Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.read more
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Journal ArticleDOI
Biological insights from 108 schizophrenia-associated genetic loci
Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Aiden Corvin,James T.R. Walters,Kai-How Farh,Peter Holmans,Phil Lee,Phil Lee,Brendan Bulik-Sullivan,Brendan Bulik-Sullivan,David A. Collier,David A. Collier,Hailiang Huang,Hailiang Huang,Tune H. Pers,Tune H. Pers,Tune H. Pers,Ingrid Agartz,Ingrid Agartz,Esben Agerbo,Esben Agerbo,Margot Albus,Madeline Alexander,Farooq Amin,Silviu Alin Bacanu,Martin Begemann,Richard A. Belliveau,Judit Bene,Sarah E. Bergen,Sarah E. Bergen,Elizabeth Bevilacqua,Tim B. Bigdeli,Donald W. Black,Richard Bruggeman,Nancy G. Buccola,Randy L. Buckner,William Byerley,Wiepke Cahn,Guiqing Cai,Dominique Campion,Rita M. Cantor,Vaughan J. Carr,Noa Carrera,Stanley V. Catts,Kimberly Chambert,Raymond C.K. Chan,Ronald Y.L. Chen,Eric Y.H. Chen,Wei Cheng,Eric F.C. Cheung,Siow Ann Chong,C. Robert Cloninger,David Cohen,Nadine Cohen,Paul Cormican,Nicholas John Craddock,James J. Crowley,David Curtis,David Curtis,Michael Davidson,Kenneth L. Davis,Franziska Degenhardt,Jurgen Del Favero,Ditte Demontis,Ditte Demontis,Dimitris Dikeos,Timothy G. Dinan,Srdjan Djurovic,Gary Donohoe,Gary Donohoe,Elodie Drapeau,Jubao Duan,Frank Dudbridge,Naser Durmishi,Peter Eichhammer,Johan G. Eriksson,Johan G. Eriksson,Valentina Escott-Price,Laurent Essioux,Ayman H. Fanous,Martilias S. Farrell,Josef Frank,Lude Franke,Robert Freedman,Nelson B. Freimer,Marion Friedl,Joseph I. Friedman,Menachem Fromer,Menachem Fromer,Menachem Fromer,Giulio Genovese,Lyudmila Georgieva,Ina Giegling,Ina Giegling,Paola Giusti-Rodríguez,Stephanie Godard,Jacqueline I. Goldstein,Jacqueline I. Goldstein,Vera Golimbet,Srihari Gopal,Jacob Gratten,Lieuwe de Haan,Christian Hammer,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Vahram Haroutunian,Vahram Haroutunian,Annette M. Hartmann,Frans Henskens,Stefan Herms,Stefan Herms,Joel N. Hirschhorn,Joel N. Hirschhorn,Per Hoffmann,Per Hoffmann,A. Hofman,Mads V. Hollegaard,David M. Hougaard,Masashi Ikeda,Inge Joa,Antonio Julià,René S. Kahn,Luba Kalaydjieva,Sena Karachanak-Yankova,Juha Karjalainen,David J. Kavanagh,Matthew C. Keller,James L. Kennedy,Andrey Khrunin,Yunjung Kim,Janis Klovins,James A. Knowles,Bettina Konte,Vaidutis Kučinskas,Zita Ausrele Kucinskiene,Hana Kuzelova-Ptackova,Anna K. Kähler,Claudine Laurent,Jimmy Lee Chee Keong,S. Hong Lee,Sophie E. Legge,Bernard Lerer,Miaoxin Li,Tao Li,Kung-Yee Liang,Jeffrey A. Lieberman,Svetlana A. Limborska,Carmel M. Loughland,Jan Lubinski,Jouko Lönnqvist,Milan Macek,Patrik K. E. Magnusson,Brion S. Maher,Wolfgang Maier,J. Mallet,Sara Marsal,Manuel Mattheisen,Manuel Mattheisen,Manuel Mattheisen,Morten Mattingsdal,Robert W. McCarley,Colm McDonald,Andrew M. McIntosh,Sandra Meier,Carin J. Meijer,Béla Melegh,Ingrid Melle,Raquelle I. Mesholam-Gately,Andres Metspalu,Patricia T. Michie,Lili Milani,Vihra Milanova,Younes Mokrab,Derek W. Morris,Derek W. Morris,Ole Mors,Ole Mors,Kieran C. Murphy,Robin M. 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Gejman,Michael Gill,Hugh Gurling,Christina M. Hultman,Nakao Iwata,Assen Jablensky,Erik G. Jönsson,Erik G. Jönsson,Kenneth S. Kendler,George Kirov,Jo Knight,Todd Lencz,Todd Lencz,Douglas F. Levinson,Qingqin S. Li,Jianjun Liu,Jianjun Liu,Anil K. Malhotra,Anil K. Malhotra,Steven A. McCarroll,Steven A. McCarroll,Andrew McQuillin,Jennifer L. Moran,Preben Bo Mortensen,Preben Bo Mortensen,Bryan J. Mowry,Markus M. Noethen,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Aarno Palotie,Aarno Palotie,Aarno Palotie,Carlos N. Pato,Tracey L. Petryshen,Tracey L. Petryshen,Danielle Posthuma,Danielle Posthuma,Marcella Rietschel,Brien P. Riley,Dan Rujescu,Dan Rujescu,Pak C. Sham,Pamela Sklar,David St Clair,Daniel R. Weinberger,Jens R. Wendland,Thomas Werge,Thomas Werge,Mark J. Daly,Mark J. Daly,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan +354 more
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Journal ArticleDOI
GCTA: a tool for genome-wide complex trait analysis.
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Common SNPs explain a large proportion of the heritability for human height
Jian Yang,Beben Benyamin,Brian P. McEvoy,Scott D. Gordon,Anjali K. Henders,Dale R. Nyholt,Pamela A. F. Madden,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael E. Goddard,Peter M. Visscher +11 more
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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Systematic localization of common disease-associated variation in regulatory DNA.
Matthew T. Maurano,Richard Humbert,Eric Rynes,Robert E. Thurman,Eric Haugen,Hao Wang,Alex Reynolds,Richard Sandstrom,Hongzhu Qu,Hongzhu Qu,Jennifer A. Brody,Anthony Shafer,Fidencio Neri,Kristen Lee,Tanya Kutyavin,Sandra Stehling-Sun,Audra K. Johnson,Theresa K. Canfield,Erika Giste,Morgan Diegel,Daniel Bates,R. Scott Hansen,Shane Neph,Peter J. Sabo,Shelly Heimfeld,Antony Raubitschek,Steven F. Ziegler,Chris Cotsapas,Nona Sotoodehnia,Ian A. Glass,Shamil R. Sunyaev,Rajinder Kaul,John A. Stamatoyannopoulos +32 more
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TL;DR: This work introduces a technique—cross-trait LD Score regression—for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap, and uses this method to estimate 276 genetic correlations among 24 traits.
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