Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium; Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium

doi:10.1016/j.cell.2018.05.046

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium, Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journal › Article › peer-review

Abstract

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. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

Original language	English
Pages (from-to)	1705-1715.
Number of pages	28
Journal	Cell
Volume	173
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2018.05.046
Publication status	Published - 14 Jun 2018

Keywords / Materials (for Non-textual outputs)

bipolar disorder
polygenic risk
psychosis
schizophrenia
subphenotypes

Access to Document

10.1016/j.cell.2018.05.046

Genomic Dissection_RUDERFER_DOA21052018_AAM_CC-BY-NC-NDAccepted author manuscript, 451 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

https://orca.cardiff.ac.uk/id/eprint/112551/Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Cite this

@article{84041389c9de44f2b744bc08f2251c99,

title = "Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes",

abstract = "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. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.",

keywords = "bipolar disorder, polygenic risk, psychosis, schizophrenia, subphenotypes",

author = "{Psychosis Endophenotypes International Consortium} and {Wellcome Trust Case Control Consortium} and {Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Ruderfer, {Douglas M.} and Stephan Ripke and Andrew McQuillin and James Boocock and Stahl, {Eli A.} and Pavlides, {Jennifer M.Whitehead} and Niamh Mullins and Charney, {Alexander W.} and Ori, {Anil P.S.} and Loohuis, {Loes M.Olde} and Enrico Domenici and {Di Florio}, Arianna and Sergi Papiol and Kalman, {Janos L.} and Vassily Trubetskoy and Rolf Adolfsson and Ingrid Agartz and Esben Agerbo and Huda Akil and Diego Albani and Margot Albus and Martin Alda and Madeline Alexander and Ney Alliey-Rodriguez and Als, {Thomas D.} and Farooq Amin and Adebayo Anjorin and Arranz, {Maria J.} and Swapnil Awasthi and Bacanu, {Silviu A.} and Badner, {Judith A.} and Marie Baekvad-Hansen and Steven Bakker and Gavin Band and Barchas, {Jack D.} and Ines Barroso and Nicholas Bass and Michael Bauer and Baune, {Bernhard T.} and Martin Begemann and Celine Bellenguez and Belliveau, {Richard A.} and Frank Bellivier and Stephan Bender and Judit Bene and Bergen, {Sarah E.} and Berrettini, {Wade H.} and Elizabeth Bevilacqua and Biernacka, {Joanna M.} and Bigdeli, {Tim B.} and Black, {Donald W.} and Hannah Blackburn and Blackwell, {Jenefer M.} and Blackwood, {Douglas H.R.} and Pedersen, {Carsten Bocker} and Michael Boehnke and Marco Boks and Borglum, {Anders D.} and Elvira Bramon and Gerome Breen and Brown, {Matthew A.} and Richard Bruggeman and Buccola, {Nancy G.} and Buckner, {Randy L.} and Monika Budde and Brendan Bulik-Sullivan and Bumpstead, {Suzannah J.} and William Bunney and Margit Burmeister and Buxbaum, {Joseph D.} and Jonas Bybjerg-Grauholm and William Byerley and Wiepke Cahn and Guiqing Cai and Cairns, {Murray J.} and Dominique Campion and Cantor, {Rita M.} and Carr, {Vaughan J.} and Noa Carrera and Casas, {Juan P.} and Miquel Casas and Catts, {Stanley V.} and Pablo Cervantes and Chambert, {Kimberley D.} and Chan, {Raymond C.K.} and Chen, {Eric Y.H.} and Chen, {Ronald Y.L.} and Wei Cheng and Cheung, {Eric F.C.} and Chong, {Siow Ann} and Clarke, {Toni Kim} and Cloninger, {C. Robert} and David Cohen and Nadine Cohen and Coleman, {Jonathan R.I.} and Collier, {David A.} and Paul Cormican and William Coryell and Nicholas Craddock and Craig, {David W.} and Benedicto Crespo-Facorro and Crowley, {James J.} and Cristiana Cruceanu and David Curtis and Czerski, {Piotr M.} and Dale, {Anders M.} and Daly, {Mark J.} and Udo Dannlowski and Ariel Darvasi and Michael Davidson and Davis, {Kenneth L.} and {de Leeuw}, {Christiaan A.} and Franziska Degenhardt and {Del Favero}, Jurgen and DeLisi, {Lynn E.} and Panos Deloukas and Ditte Demontis and DePaulo, {J. Raymond} and {di Forti}, Marta and Dimitris Dikeos and Timothy Dinan and Srdjan Djurovic and Dobbyn, {Amanda L.} and Peter Donnelly and Gary Donohoe and Elodie Drapeau and Serge Dronov and Jubao Duan and Frank Dudbridge and Audrey Duncanson and Howard Edenberg and Sarah Edkins and Hannelore Ehrenreich and Peter Eichhammer and Torbjorn Elvsashagen and Johan Eriksson and Valentina Escott-Price and Tonu Esko and Laurent Essioux and Bruno Etain and Fan, {Chun Chieh} and Farh, {Kai How} and Farrell, {Martilias S.} and Matthew Flickinger and Foroud, {Tatiana M.} and Liz Forty and Josef Frank and Lude Franke and Christine Fraser and Robert Freedman and Colin Freeman and Freimer, {Nelson B.} and Friedman, {Joseph I.} and Menachem Fromer and Frye, {Mark A.} and Fullerton, {Janice M.} and Katrin Gade and Julie Garnham and Gaspar, {Helena A.} and Gejman, {Pablo V.} and Giulio Genovese and Lyudmila Georgieva and Claudia Giambartolomei and Eleni Giannoulatou and Ina Giegling and Michael Gill and Matthew Gillman and Pedersen, {Marianne Giortz} and Paola Giusti-Rodriguez and Stephanie Godard and Fernando Goes and Goldstein, {Jacqueline I.} and Srihari Gopal and Gordon, {Scott D.} and Katherine Gordon-Smith and Jacob Gratten and Emma Gray and Green, {Elaine K.} and Green, {Melissa J.} and Greenwood, {Tiffany A.} and Maria Grigoroiu-Serbanescu and Jakob Grove and Weihua Guan and Hugh Gurling and Parra, {Jose Guzman} and Rhian Gwilliam and {de Haan}, Lieuwe and Jeremy Hall and Hall, {Mei Hua} and Christian Hammer and Naomi Hammond and Hamshere, {Marian L.} and Mark Hansen and Thomas Hansen and Vahram Haroutunian and Hartmann, {Annette M.} and Joanna Hauser and Martin Hautzinger and Urs Heilbronner and Garrett Hellenthal and Henskens, {Frans A.} and Stefan Herms and Maria Hipolito and Hirschhorn, {Joel N.} and Per Hoffmann and Hollegaard, {Mads V.} and Hougaard, {David M.} and Hailiang Huang and Laura Huckins and Hultman, {Christina M.} and Hunt, {Sarah E.} and Masashi Ikeda and Nakao Iwata and Conrad Iyegbe and Kendler, {Kenneth S.} and Stephane Jamain and Janusz Jankowski and Alagurevathi Jayakumar and Inge Joa and Ian Jones and Jones, {Lisa A.} and Jonsson, {Erik G.} and Antonio Julia and Anders Jureus and Kahler, {Anna K.} and Kahn, {Rene S.} and Luba Kalaydjieva and Radhika Kandaswamy and Sena Karachanak-Yankova and Juha Karjalainen and Robert Karlsson and David Kavanagh and Keller, {Matthew C.} and Kelly, {Brian J.} and John Kelsoe and Kennedy, {James L.} and Andrey Khrunin and Yunjung Kim and George Kirov and Sarah Kittel-Schneider and Janis Klovins and Jo Knight and Knott, {Sarah V.} and Knowles, {James A.} and Manolis Kogevinas and Bettina Konte and Eugenia Kravariti and Vaidutis Kucinskas and Kucinskiene, {Zita Ausrele} and Ralph Kupka and Hana Kuzelova-Ptackova and Mikael Landen and Cordelia Langford and Claudine Laurent and Jacob Lawrence and Stephen Lawrie and Lawson, {William B.} and Markus Leber and Marion Leboyer and Lee, {Phil H.} and Keong, {Jimmy Lee Chee} and Legge, {Sophie E.} and Todd Lencz and Bernard Lerer and Levinson, {Douglas F.} and Levy, {Shawn E.} and Lewis, {Cathryn M.} and Li, {Jun Z.} and Miaoxin Li and Li, {Qingqin S.} and Tao Li and Liang, {Kung Yee} and Jennifer Liddle and Jeffrey Lieberman and Svetlana Limborska and Kuang Lin and Linszen, {Don H.} and Jolanta Lissowska and Chunyu Liu and Jianjun Liu and Jouko Lonnqvist and Loughland, {Carmel M.} and Jan Lubinski and Susanne Lucae and Milan Macek and MacIntyre, {Donald J.} and Magnusson, {Patrik K.E.} and Maher, {Brion S.} and Mahon, {Pamela B.} and Wolfgang Maier and Malhotra, {Anil K.} and Jacques Mallet and Malt, {Ulrik F.} and Markus, {Hugh S.} and Sara Marsal and Martin, {Nicholas G.} and Ignacio Mata and Mathew, {Christopher G.} and Manuel Mattheisen and Morten Mattingsdal and Fermin Mayoral and McCann, {Owen T.} and McCarley, {Robert W.} and McCarroll, {Steven A.} and McCarthy, {Mark I.} and Colm McDonald and McElroy, {Susan L.} and Peter McGuffin and McInnis, {Melvin G.} and McIntosh, {Andrew M.} and McKay, {James D.} and McMahon, {Francis J.} and Helena Medeiros and Medland, {Sarah E.} and Sandra Meier and Meijer, {Carin J.} and Bela Melegh and Ingrid Melle and Fan Meng and Mesholam-Gately, {Raquelle I.} and Andres Metspalu and Michie, {Patricia T.} and Lili Milani and Vihra Milanova and Mitchell, {Philip B.} and Younes Mokrab and Montgomery, {Grant W.} and Moran, {Jennifer L.} and Gunnar Morken and Morris, {Derek W.} and Ole Mors and Mortensen, {Preben B.} and Mowry, {Bryan J.} and M{\"u}hleisen, {Thomas W.} and Bertram M{\"u}ller-Myhsok and Murphy, {Kieran C.} and Murray, {Robin M.} and Myers, {Richard M.} and Inez Myin-Germeys and Neale, {Benjamin M.} and Mari Nelis and Igor Nenadic and Nertney, {Deborah A.} and Gerald Nestadt and Nicodemus, {Kristin K.} and Nievergelt, {Caroline M.} and Liene Nikitina-Zake and Vishwajit Nimgaonkar and Laura Nisenbaum and Merete Nordentoft and Annelie Nordin and N{\"o}then, {Markus M.} and Nwulia, {Evaristus A.} and Eadbhard O'Callaghan and Claire O'Donovan and Colm O'Dushlaine and O'Neill, {F. Anthony} and Oedegaard, {Ketil J.} and Oh, {Sang Yun} and Ann Olincy and Line Olsen and Lilijana Oruc and {Van Os}, Jim and Owen, {Michael J.} and Paciga, {Sara A.} and Palmer, {Colin N.A.} and Aarno Palotie and Christos Pantelis and Papadimitriou, {George N.} and Elena Parkhomenko and Carlos Pato and Pato, {Michele T.} and Tiina Paunio and Richard Pearson and Perkins, {Diana O.} and Perlis, {Roy H.} and Amy Perry and Pers, {Tune H.} and Petryshen, {Tracey L.} and Andrea Pfennig and Marco Picchioni and Olli Pietilainen and Jonathan Pimm and Matti Pirinen and Robert Plomin and Pocklington, {Andrew J.} and Danielle Posthuma and Potash, {James B.} and Potter, {Simon C.} and John Powell and Alkes Price and Pulver, {Ann E.} and Purcell, {Shaun M.} and Digby Quested and Ramos-Quiroga, {Josep Antoni} and Rasmussen, {Henrik B.} and Anna Rautanen and Radhi Ravindrarajah and Regeer, {Eline J.} and Abraham Reichenberg and Andreas Reif and Reimers, {Mark A.} and Marta Ribases and Rice, {John P.} and Richards, {Alexander L.} and Michelle Ricketts and Riley, {Brien P.} and Fabio Rivas and Margarita Rivera and Roffman, {Joshua L.} and Rouleau, {Guy A.} and Panos Roussos and Dan Rujescu and Veikko Salomaa and Cristina Sanchez-Mora and Sanders, {Alan R.} and Sawcer, {Stephen J.} and Ulrich Schall and Schatzberg, {Alan F.} and Scheftner, {William A.} and Schofield, {Peter R.} and Schork, {Nicholas J.} and Schwab, {Sibylle G.} and Scolnick, {Edward M.} and Scott, {Laura J.} and Scott, {Rodney J.} and Seidman, {Larry J.} and Alessandro Serretti and Sham, {Pak C.} and Weickert, {Cynthia Shannon} and Tatyana Shehktman and Jianxin Shi and Shilling, {Paul D.} and Engilbert Sigurdsson and Silverman, {Jeremy M.} and Kang Sim and Claire Slaney and Petr Slominsky and Smeland, {Olav B.} and Smoller, {Jordan W.} and So, {Hon Cheong} and Sobell, {Janet L.} and Erik Soderman and Hansen, {Christine Soholm} and Spencer, {Chris C.A.} and Spijker, {Anne T.} and {St Clair}, David and Hreinn Stefansson and Kari Stefansson and Stacy Steinberg and Elisabeth Stogmann and Eystein Stordal and Amy Strange and Straub, {Richard E.} and Strauss, {John S.} and Fabian Streit and Eric Strengman and Jana Strohmaier and Stroup, {T. 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Hong} and O'Donovan, {Michael C.} and Sullivan, {Patrick F.} and Ophoff, {Roel A.} and Wray, {Naomi R.} and Pamela Sklar and Kendler, {Kenneth S.}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = jun,

day = "14",

doi = "10.1016/j.cell.2018.05.046",

language = "English",

volume = "173",

pages = "1705--1715.",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "7",

}

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. / Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium; Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium.
In: Cell, Vol. 173, No. 7, 14.06.2018, p. 1705-1715.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

AU - Psychosis Endophenotypes International Consortium

AU - Wellcome Trust Case Control Consortium

AU - Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Ruderfer, Douglas M.

AU - Ripke, Stephan

AU - McQuillin, Andrew

AU - Boocock, James

AU - Stahl, Eli A.

AU - Pavlides, Jennifer M.Whitehead

AU - Mullins, Niamh

AU - Charney, Alexander W.

AU - Ori, Anil P.S.

AU - Loohuis, Loes M.Olde

AU - Domenici, Enrico

AU - Di Florio, Arianna

AU - Papiol, Sergi

AU - Kalman, Janos L.

AU - Trubetskoy, Vassily

AU - Adolfsson, Rolf

AU - Agartz, Ingrid

AU - Agerbo, Esben

AU - Akil, Huda

AU - Albani, Diego

AU - Albus, Margot

AU - Alda, Martin

AU - Alexander, Madeline

AU - Alliey-Rodriguez, Ney

AU - Als, Thomas D.

AU - Amin, Farooq

AU - Anjorin, Adebayo

AU - Arranz, Maria J.

AU - Awasthi, Swapnil

AU - Bacanu, Silviu A.

AU - Badner, Judith A.

AU - Baekvad-Hansen, Marie

AU - Bakker, Steven

AU - Band, Gavin

AU - Barchas, Jack D.

AU - Barroso, Ines

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Baune, Bernhard T.

AU - Begemann, Martin

AU - Bellenguez, Celine

AU - Belliveau, Richard A.

AU - Bellivier, Frank

AU - Bender, Stephan

AU - Bene, Judit

AU - Bergen, Sarah E.

AU - Berrettini, Wade H.

AU - Bevilacqua, Elizabeth

AU - Biernacka, Joanna M.

AU - Bigdeli, Tim B.

AU - Black, Donald W.

AU - Blackburn, Hannah

AU - Blackwell, Jenefer M.

AU - Blackwood, Douglas H.R.

AU - Pedersen, Carsten Bocker

AU - Boehnke, Michael

AU - Boks, Marco

AU - Borglum, Anders D.

AU - Bramon, Elvira

AU - Breen, Gerome

AU - Brown, Matthew A.

AU - Bruggeman, Richard

AU - Buccola, Nancy G.

AU - Buckner, Randy L.

AU - Budde, Monika

AU - Bulik-Sullivan, Brendan

AU - Bumpstead, Suzannah J.

AU - Bunney, William

AU - Burmeister, Margit

AU - Buxbaum, Joseph D.

AU - Bybjerg-Grauholm, Jonas

AU - Byerley, William

AU - Cahn, Wiepke

AU - Cai, Guiqing

AU - Cairns, Murray J.

AU - Campion, Dominique

AU - Cantor, Rita M.

AU - Carr, Vaughan J.

AU - Carrera, Noa

AU - Casas, Juan P.

AU - Casas, Miquel

AU - Catts, Stanley V.

AU - Cervantes, Pablo

AU - Chambert, Kimberley D.

AU - Chan, Raymond C.K.

AU - Chen, Eric Y.H.

AU - Chen, Ronald Y.L.

AU - Cheng, Wei

AU - Cheung, Eric F.C.

AU - Chong, Siow Ann

AU - Clarke, Toni Kim

AU - Cloninger, C. Robert

AU - Cohen, David

AU - Cohen, Nadine

AU - Coleman, Jonathan R.I.

AU - Collier, David A.

AU - Cormican, Paul

AU - Coryell, William

AU - Craddock, Nicholas

AU - Craig, David W.

AU - Crespo-Facorro, Benedicto

AU - Crowley, James J.

AU - Cruceanu, Cristiana

AU - Curtis, David

AU - Czerski, Piotr M.

AU - Dale, Anders M.

AU - Daly, Mark J.

AU - Dannlowski, Udo

AU - Darvasi, Ariel

AU - Davidson, Michael

AU - Davis, Kenneth L.

AU - de Leeuw, Christiaan A.

AU - Degenhardt, Franziska

AU - Del Favero, Jurgen

AU - DeLisi, Lynn E.

AU - Deloukas, Panos

AU - Demontis, Ditte

AU - DePaulo, J. Raymond

AU - di Forti, Marta

AU - Dikeos, Dimitris

AU - Dinan, Timothy

AU - Djurovic, Srdjan

AU - Dobbyn, Amanda L.

AU - Donnelly, Peter

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AU - Dronov, Serge

AU - Duan, Jubao

AU - Dudbridge, Frank

AU - Duncanson, Audrey

AU - Edenberg, Howard

AU - Edkins, Sarah

AU - Ehrenreich, Hannelore

AU - Eichhammer, Peter

AU - Elvsashagen, Torbjorn

AU - Eriksson, Johan

AU - Escott-Price, Valentina

AU - Esko, Tonu

AU - Essioux, Laurent

AU - Etain, Bruno

AU - Fan, Chun Chieh

AU - Farh, Kai How

AU - Farrell, Martilias S.

AU - Flickinger, Matthew

AU - Foroud, Tatiana M.

AU - Forty, Liz

AU - Frank, Josef

AU - Franke, Lude

AU - Fraser, Christine

AU - Freedman, Robert

AU - Freeman, Colin

AU - Freimer, Nelson B.

AU - Friedman, Joseph I.

AU - Fromer, Menachem

AU - Frye, Mark A.

AU - Fullerton, Janice M.

AU - Gade, Katrin

AU - Garnham, Julie

AU - Gaspar, Helena A.

AU - Gejman, Pablo V.

AU - Genovese, Giulio

AU - Georgieva, Lyudmila

AU - Giambartolomei, Claudia

AU - Giannoulatou, Eleni

AU - Giegling, Ina

AU - Gill, Michael

AU - Gillman, Matthew

AU - Pedersen, Marianne Giortz

AU - Giusti-Rodriguez, Paola

AU - Godard, Stephanie

AU - Goes, Fernando

AU - Goldstein, Jacqueline I.

AU - Gopal, Srihari

AU - Gordon, Scott D.

AU - Gordon-Smith, Katherine

AU - Gratten, Jacob

AU - Gray, Emma

AU - Green, Elaine K.

AU - Green, Melissa J.

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AU - Grove, Jakob

AU - Guan, Weihua

AU - Gurling, Hugh

AU - Parra, Jose Guzman

AU - Gwilliam, Rhian

AU - de Haan, Lieuwe

AU - Hall, Jeremy

AU - Hall, Mei Hua

AU - Hammer, Christian

AU - Hammond, Naomi

AU - Hamshere, Marian L.

AU - Hansen, Mark

AU - Hansen, Thomas

AU - Haroutunian, Vahram

AU - Hartmann, Annette M.

AU - Hauser, Joanna

AU - Hautzinger, Martin

AU - Heilbronner, Urs

AU - Hellenthal, Garrett

AU - Henskens, Frans A.

AU - Herms, Stefan

AU - Hipolito, Maria

AU - Hirschhorn, Joel N.

AU - Hoffmann, Per

AU - Hollegaard, Mads V.

AU - Hougaard, David M.

AU - Huang, Hailiang

AU - Huckins, Laura

AU - Hultman, Christina M.

AU - Hunt, Sarah E.

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Iyegbe, Conrad

AU - Kendler, Kenneth S.

AU - Jamain, Stephane

AU - Jankowski, Janusz

AU - Jayakumar, Alagurevathi

AU - Joa, Inge

AU - Jones, Ian

AU - Jones, Lisa A.

AU - Jonsson, Erik G.

AU - Julia, Antonio

AU - Jureus, Anders

AU - Kahler, Anna K.

AU - Kahn, Rene S.

AU - Kalaydjieva, Luba

AU - Kandaswamy, Radhika

AU - Karachanak-Yankova, Sena

AU - Karjalainen, Juha

AU - Karlsson, Robert

AU - Kavanagh, David

AU - Keller, Matthew C.

AU - Kelly, Brian J.

AU - Kelsoe, John

AU - Kennedy, James L.

AU - Khrunin, Andrey

AU - Kim, Yunjung

AU - Kirov, George

AU - Kittel-Schneider, Sarah

AU - Klovins, Janis

AU - Knight, Jo

AU - Knott, Sarah V.

AU - Knowles, James A.

AU - Kogevinas, Manolis

AU - Konte, Bettina

AU - Kravariti, Eugenia

AU - Kucinskas, Vaidutis

AU - Kucinskiene, Zita Ausrele

AU - Kupka, Ralph

AU - Kuzelova-Ptackova, Hana

AU - Landen, Mikael

AU - Langford, Cordelia

AU - Laurent, Claudine

AU - Lawrence, Jacob

AU - Lawrie, Stephen

AU - Lawson, William B.

AU - Leber, Markus

AU - Leboyer, Marion

AU - Lee, Phil H.

AU - Keong, Jimmy Lee Chee

AU - Legge, Sophie E.

AU - Lencz, Todd

AU - Lerer, Bernard

AU - Levinson, Douglas F.

AU - Levy, Shawn E.

AU - Lewis, Cathryn M.

AU - Li, Jun Z.

AU - Li, Miaoxin

AU - Li, Qingqin S.

AU - Li, Tao

AU - Liang, Kung Yee

AU - Liddle, Jennifer

AU - Lieberman, Jeffrey

AU - Limborska, Svetlana

AU - Lin, Kuang

AU - Linszen, Don H.

AU - Lissowska, Jolanta

AU - Liu, Chunyu

AU - Liu, Jianjun

AU - Lonnqvist, Jouko

AU - Loughland, Carmel M.

AU - Lubinski, Jan

AU - Lucae, Susanne

AU - Macek, Milan

AU - MacIntyre, Donald J.

AU - Magnusson, Patrik K.E.

AU - Maher, Brion S.

AU - Mahon, Pamela B.

AU - Maier, Wolfgang

AU - Malhotra, Anil K.

AU - Mallet, Jacques

AU - Malt, Ulrik F.

AU - Markus, Hugh S.

AU - Marsal, Sara

AU - Martin, Nicholas G.

AU - Mata, Ignacio

AU - Mathew, Christopher G.

AU - Mattheisen, Manuel

AU - Mattingsdal, Morten

AU - Mayoral, Fermin

AU - McCann, Owen T.

AU - McCarley, Robert W.

AU - McCarroll, Steven A.

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PY - 2018/6/14

Y1 - 2018/6/14

N2 - 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. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

AB - 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. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

KW - bipolar disorder

KW - polygenic risk

KW - psychosis

KW - schizophrenia

KW - subphenotypes

UR - http://www.scopus.com/inward/record.url?scp=85048172948&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2018.05.046

DO - 10.1016/j.cell.2018.05.046

M3 - Article

C2 - 29906448

AN - SCOPUS:85048172948

SN - 0092-8674

VL - 173

SP - 1705-1715.

JO - Cell

JF - Cell

IS - 7

ER -

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

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