Open AccessGenomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
Author(s) -
Douglas M. Ruderfer,
Stephan Ripke,
Andrew McQuillin,
James Boocock,
Eli A. Stahl,
Jennifer M. Whitehead Pavlides,
Niamh Mullins,
Alexander W. Charney,
Anil P. S. Ori,
Loes M. Olde Loohuis,
Enrico Domenici,
Arianna Di Florio,
Sergi Papiol,
János Kálmán,
Vassily Trubetskoy,
Rolf Adolfsson,
Ingrid Agartz,
Esben Agerbo,
Huda Akil,
Diego Albani,
Margot Albus,
Martin Alda,
Madeline Alexander,
Ney AllieyRodriguez,
Thomas D. Als,
Farooq Amin,
Adebayo Anjorin,
María J. Arranz,
Swapnil Awasthi,
SilviuAlin Bacanu,
Judith A. Badner,
Marie BækvadHansen,
Steven C. Bakker,
Gavin Band,
Jack D. Barchas,
Inês Barroso,
Nicholas Bass,
Michael Bauer,
Bernhard T. Baune,
Martin Begemann,
Céline Bellenguez,
Richard A. Belliveau,
Frank Bellivier,
Stephan Bender,
Judit Bene,
Sarah E. Bergen,
Wade H. Berrettini,
Elizabeth Bevilacqua,
Joanna M. Biernacka,
Tim B. Bigdeli,
Donald W. Black,
Hannah Blackburn,
Jenefer M. Blackwell,
Douglas Blackwood,
Carsten Bøcker Pedersen,
Michael Boehnke,
Marco P. Boks,
Anders D. Børglum,
Elvira Bramon,
Gerome Breen,
Matthew A. Brown,
Richard Bruggeman,
Nancy G. Buccola,
Randy L. Buckner,
Monika Budde,
Brendan BulikSullivan,
Suzannah J. Bumpstead,
William E. Bunney,
Margit Burmeister,
Joseph D. Buxbaum,
Jonas BybjergGrauholm,
William Byerley,
Wiepke Cahn,
Guiqing Cai,
Murray J. Cairns,
Dominique Campion,
Rita M. Cantor,
Vaughan J. Carr,
Noa Carrera,
Juan P. Casas,
Miguel Casas,
Stanley V. Catts,
Pablo Cervantes,
Kimberley D. Chambert,
Raymond C. K. Chan,
Eric Chen,
Ronald Y.L. Chen,
Wei Cheng,
Eric F.C. Cheung,
Siow Ann Chong,
ToniKim Clarke,
C. Robert Cloninger,
David Cohen,
Nadine Cohen,
Jonathan R. I. Coleman,
David Collier,
Paul Cormican,
William Coryell,
Nicholas John Craddock,
David W. Craig,
Benedicto CrespoFacorro,
James J. Crowley,
Cristiana Cruceanu,
David Curtis,
Piotr M. Czerski,
Anders M. Dale,
Mark J. Daly,
Udo Dannlowski,
Ariel Darvasi,
Michael Davidson,
Kenneth L. Davis,
Christiaan de Leeuw,
Franziska Degenhardt,
Jurgen DelFavero,
Lynn E. DeLisi,
Panos Deloukas,
Ditte Demontis,
J. Raymond DePaulo,
Marta Di Forti,
Dimitris Dikeos,
Timothy G. Dinan,
Srdjan Djurovic,
Amanda Dobbyn,
Peter Donnelly,
Gary Donohoe,
Elodie Drapeau,
Serge Dronov,
Jubao Duan,
Frank Dudbridge,
Audrey Duncanson,
Howard J. Edenberg,
Sarah Edkins,
Hannelore Ehrenreich,
Peter Eichhammer,
Torbjørn Elvsåshagen,
Johan G. Eriksson,
Valentina EscottPrice,
Tõnu Esko,
Laurent Essioux,
Bruno Étain,
Chun Chieh Fan,
Kai-How Farh,
Martilias S. Farrell,
Matthew Flickinger,
Tatiana Foroud,
Liz Forty,
Josef Frank,
Lude Franke,
Christine Fraser,
Robert Freedman,
Colin Freeman,
Nelson B. Freimer,
Joseph I. Friedman,
Menachem Fromer,
Mark A. Frye,
Janice M. Fullerton,
Katrin Gade,
Julie Garnham,
Héléna A. Gaspar,
Pablo V. Gejman,
Giulio Genovese,
Lyudmila Georgieva,
Claudia Giambartolomei,
Eleni Giannoulatou,
Ina Giegling,
Michael Gill,
Matthew Gillman,
Marianne Giørtz Pedersen,
Paola GiustiRodríguez,
Stephanie Godard,
Fernando S. Goes,
Jacqueline I. Goldstein,
Srihari Gopal,
Scott D. Gordon,
Katherine GordonSmith,
Jacob Gratten,
Emma Gray,
Elaine Green,
Melissa J. Green,
Tiffany A. Greenwood,
Maria GrigoroiuSerbânescu,
Jakob Grove,
Weihua Guan,
Hugh Gurling,
José GuzmánParra,
Rhian Gwilliam,
Lieuwe de Haan,
Jérémy Hall,
MeiHua Hall,
Christian Hammer,
Naomi Hammond,
Marian L. Hamshere,
Thomas Hansen,
Vahram Haroutunian,
Annette M. Hartmann,
Joanna Hauser,
Martin Hautzinger,
Urs Heilbronner,
Garrett Hellenthal,
Frans A. Henskens,
Stefan Herms,
Maria Hipolito,
Joel N. Hirschhorn,
Per Hoffmann,
Mads V. Hollegaard,
David M. Hougaard,
Hailiang Huang,
Laura M. Huckins,
Christina M. Hultman,
Sarah Hunt,
Masashi Ikeda,
Nakao Iwata,
Conrad Iyegbe,
Assen Jablensky,
Stéphane Jamain,
Janusz Jankowski,
Alagurevathi Jayakumar,
Inge Joa,
Ian Jones,
Lisa Jones,
Erik G. Jönsson,
Antonio Julià,
Anders Juréus,
Anna K. Kähler,
René S. Kahn,
Luba Kalaydjieva,
Radhika Kandaswamy,
Sena Karachanak-Yankova,
Juha Karjalainen,
Robert Karlsson,
David Kavanagh,
Matthew C. Keller,
Brian Kelly,
John R. Kelsoe,
James L. Kennedy,
Andrey Khrunin,
Yunjung Kim,
George Kirov,
Sarah KittelSchneider,
Jānis Kloviņš,
Jo Knight,
Sarah Knott,
James A. Knowles,
Manolis Kogevinas,
Bettina Konte,
Eugenia Kravariti,
Vaidutis Kučinskas,
Zita Aušrelė Kučinskienė,
Ralph Kupka,
Hana Kuzelova-Ptackova,
Mikael Landén,
Cordelia Langford,
Claudine Laurent,
Jacob Lawrence,
Stephen M. Lawrie,
William Lawson,
Markus Leber,
Marion Leboyer,
Phil H. Lee,
Jimmy Lee,
Sophie E. Legge,
Todd Lencz,
Bernard Lerer,
Douglas F. Levinson,
Shawn Levy,
Cathryn M. Lewis,
Jun Z. Li,
Miaoxin Li,
Qingqin S. Li,
Tao Li,
KungYee Liang,
Jennifer Liddle,
Jeffrey A. Lieberman,
Limborskaia Sa,
Kuang Lin,
Don Linszen,
Jolanta Lissowska,
Chunyu Liu,
Jianjun Liu,
Jouko Lönnqvist,
Carmel M. Loughland,
Jan Lubiński,
Susanne Lucae,
Milan Maçek,
Donald J. MacIntyre,
Patrik K. E. Magnusson,
Brion S. Maher,
Pamela B. Mahon,
Wolfgang Maier,
Anil K. Malhotra,
Jacques Mallet,
Ulrik Fredrik Malt,
Hugh S. Markus,
Sara Marsal,
Nicholas G. Martin,
Ignácio F. Mata,
Christopher G. Mathew,
Manuel Mattheisen,
Morten Mattingsdal,
Fermín Mayoral,
Owen T McCann,
Robert W. McCarley,
Steven A. McCarroll,
Mark I. McCarthy,
Colm McDonald,
Susan L. McElroy,
Peter McGuffin,
Melvin G. McInnis,
Andrew M. McIntosh,
James McKay,
Francis J. McMahon,
Helena Medeiros,
Sarah E. Medland,
Sandra Meier,
Carin J. Meijer,
Béla Melegh,
Ingrid Melle,
Fan Meng,
Raquelle I. MesholamGately,
Andres Metspalu,
Patricia T. Michie,
Lili Milani,
Vihra Milanova,
Philip B. Mitchell,
Younes Mokrab,
Grant W. Montgomery,
Jennifer L. Moran,
Gunnar Morken,
Derek W. Morris,
Ole Mors,
Preben Bo Mortensen,
Bryan Mowry,
Thomas W. Mühleisen,
Bertram MüllerMyhsok,
Kieran C. Murphy,
Robin M. Murray,
R Myers,
Inez MyinGermeys,
Benjamin M. Neale,
Mari Nelis,
Igor Nenadić,
Deborah A. Nertney,
Gerald Nestadt,
Kristin K. Nicodemus,
Caroline M. Nievergelt,
Liene Ņikitina-Zaķe,
Vishwajit L. Nimgaonkar,
Laura Nisenbaum,
Merete Nordentoft,
Annelie Nordin,
Markus M. Nöthen,
Evaristus A. Nwulia,
Eadbhard O’Callaghan,
Claire O’Donovan,
Colm O’Dushlaine,
F. Anthony O’Neill,
Ketil J. Øedegaard,
Sang-Yun Oh,
Ann Olincy,
Line Olsen,
Lilijana Oruč,
Jim van Os,
Michael J. Owen,
Sara A. Paciga,
Nicholette D. Palmer,
Aarno Palotie,
Christos Pantelis,
George N. Papadimitriou,
Elena Parkhomenko,
Carlos N. Pato,
Michele T. Pato,
Tiina Paunio,
Richard D. Pearson,
Diana O. Perkins,
Roy H. Perlis,
Amy Perry,
Tune H. Pers,
Tracey L. Petryshen,
Andrea Pfennig,
Marco Picchioni,
Olli Pietiläinen,
Jonathan Pimm,
Matti Pirinen,
Robert Plomin,
Andrew Pocklington,
Daniëlle Posthuma,
James B. Potash,
Simon Potter,
John Powell,
Alkes L. Price,
Ann E. Pulver,
Shaun Purcell,
Digby Quested,
Josep Antoni RamosQuiroga,
Henrik Berg Rasmussen,
Anna Rautanen,
Rathi Ravindrarajah,
Eline J. Regeer,
Abraham Reichenberg,
Andreas Reif,
Mark A. Reimers,
Marta Ribasés,
John P. Rice,
Alexander Richards,
Michelle Ricketts,
Brien P. Riley,
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Margarita Rivera,
Joshua L. Roffman,
Guy A. Rouleau,
Panos Roussos,
Dan Rujescu,
Veikko Salomaa,
Cristina SánchezMora,
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Stephen Sawcer,
Ulrich Schall,
Alan F. Schatzberg,
William A. Scheftner,
Peter R. Schofield,
Nicholas J. Schork,
Sibylle G. Schwab,
Edward M. Scolnick,
Laura J. Scott,
Rodney J. Scott,
Larry J. Seidman,
Alessandro Serretti,
Pak C. Sham,
Cynthia Shan Weickert,
Tatyana Shehktman,
Jianxin Shi,
Paul D. Shilling,
Engilbert Sigurðsson,
Jeremy M. Silverman,
Kang Sim,
Claire Slaney,
P. A. Slominsky,
Olav B. Smeland,
Jordan W. Smoller,
HonCheong So,
Janet L. Sobell,
Erik Söderman,
Christine Søholm Hansen,
Chris C. A. Spencer,
Anne T. Spijker,
David St Clair,
Hreinn Stefánsson,
Kári Stéfansson,
Stacy Steinberg,
Elisabeth Stögmann,
Eystein Stordal,
Amy Strange,
Richard E. Straub,
John S. Strauss,
Fabian Streit,
Eric Strengman,
Jana Strohmaier,
T. Scott Stroup,
Zhan Su,
Mythily Subramaniam,
Jaana Suvisaari,
Dragan M. Švrakić,
Jin P. Szatkiewicz,
Szabolcs Szelinger,
Avazeh Tashakkori-Ghanbaria,
Srinivas Thirumalai,
Robert C. Thompson,
Thorgeir E. Thorgeirsson,
Драга Тончева,
Paul A. Tooney,
Sarah Tosato,
Timothea Toulopoulou,
Richard C. Trembath,
Jens Treutlein,
Gustavo Turecki,
Arne E. Vaaler,
Helmut Vedder,
Eduard Vieta,
John B. Vincent,
Peter M. Visscher,
Ananth C. Viswanathan,
Damjan Vukcevic,
John L. Waddington,
Matthew Waller,
Dermot Walsh,
Muriel Walshe,
James Walters,
Dai Wang,
Qiang Wang,
Weiqing Wang,
Yunpeng Wang,
Stanley J. Watson,
Bradley T. Webb,
Thomas W. Weickert,
Daniel R. Weinberger,
Matthias Weisbrod,
Mark Weiser,
Thomas Werge,
Paul A. Weston,
Pamela Whittaker,
Sara Widaa,
Durk Wiersma,
Dieter B. Wildenauer,
Nigel Williams,
Stephanie Williams,
Stephanie H. Witt,
Aaron R. Wolen,
Emily H. M. Wong,
Nicholas Wood,
Brandon K. Wormley,
Jing Qin Wu,
Simon Xi,
Wei Xu,
Allan H. Young,
Clement C. Zai,
Peter P. Zandi,
Peng Zhang,
Xuebin Zheng,
Fritz Zimprich,
Sebastian Zöllner,
Aiden Corvin,
Ayman H. Fanous,
Sven Cichon,
Marcella Rietschel,
Elliot S. Gershon,
Thomas G. Schulze,
Alfredo B. CuéllarBarboza,
Andreas J. Forstner,
Peter Holmans,
John I. Nürnberger,
Ole A. Andreassen,
Sang Lee,
Michael O’Donovan,
Patrick F. Sullivan,
Roel A. Ophoff,
Naomi R. Wray,
Pamela Sklar,
Kenneth S. Kendler
Publication year - 2018
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2018.05.046
Subject(s) - bipolar disorder , schizophrenia (object oriented programming) , biology , genome wide association study , genetics , gene , psychiatry , single nucleotide polymorphism , neuroscience , psychology , genotype , cognition
Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.
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