Analysis of shared heritability in common disorders of the brain

The Brainstorm Consortium; Sarah Cohen-Woods

doi:10.1126/science.aap8757

Analysis of shared heritability in common disorders of the brain

The Brainstorm Consortium, Sarah Cohen-Woods

College of Education, Psychology and Social Work

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

1406 Citations (Scopus)

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Original language	English
Article number	eaap8757
Number of pages	15
Journal	Science
Volume	360
Issue number	6395
DOIs	https://doi.org/10.1126/science.aap8757
Publication status	Published - 22 Jun 2018

Keywords

Brain disorders
genetic risks
genomics
comorbidity

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10.1126/science.aap8757Licence: In Copyright

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@article{56fd23cee4414e2eb09336bee96643e8,

title = "Analysis of shared heritability in common disorders of the brain",

abstract = "Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.",

keywords = "Brain disorders, genetic risks, genomics, comorbidity",

author = "{The Brainstorm Consortium} and Verneri Anttila and Brendan Bulik-Sullivan and Finucane, {Hilary K.} and Walters, {Raymond K.} and Jose Bras and Laramie Duncan and Valentina Escott-Price and Falcone, {Guido J.} and Padhraig Gormley and Rainer Malik and Patsopoulos, {Nikolaos A.} and Stephan Ripke and Zhi Wei and Dongmei Yu and Lee, {Phil H.} and Patrick Turley and Benjamin Grenier-Boley and Vincent Chouraki and Yoichiro Kamatani and Claudine Berr and Luc Letenneur and Didier Hannequin and Philippe Amouyel and Anne Boland and Deleuze, {Jean Fran{\c c}ois} and Emmanuelle Duron and Vardarajan, {Badri N.} and Christiane Reitz and Goate, {Alison M.} and Huentelman, {Matthew J.} and {Ilyas Kamboh}, M. and Larson, {Eric B.} and Ekaterina Rogaeva and George-Hyslop, {Peter St} and Hakon Hakonarson and Kukull, {Walter A.} and Farrer, {Lindsay A.} and Barnes, {Lisa L.} and Beach, {Thomas G.} and {Yesim Demirci}, F. and Elizabeth Head and Hulette, {Christine M.} and Jicha, {Gregory A.} and Kauwe, {John S.K.} and Kaye, {Jeffrey A.} and Leverenz, {James B.} and Levey, {Allan I.} and Lieberman, {Andrew P.} and Pankratz, {Vernon S.} and Poon, {Wayne W.} and Quinn, {Joseph F.} and Saykin, {Andrew J.} and Schneider, {Lon S.} and Smith, {Amanda G.} and Sonnen, {Joshua A.} and Stern, {Robert A.} and {Van Deerlin}, {Vivianna M.} and {Van Eldik}, {Linda J.} and Denise Harold and Giancarlo Russo and Rubinsztein, {David C.} and Anthony Bayer and Magda Tsolaki and Petra Proitsi and Fox, {Nick C.} and Harald Hampel and Owen, {Michael J.} and Simon Mead and Peter Passmore and Kevin Morgan and N{\"o}then, {Markus M.} and Schott, {Jonathan M.} and Martin Rossor and Lupton, {Michelle K.} and Per Hoffmann and Johannes Kornhuber and Brian Lawlor and Andrew McQuillin and Ammar Al-Chalabi and Bis, {Joshua C.} and Agustin Ruiz and Merc{\`e} Boada and Sudha Seshadri and Alexa Beiser and Kenneth Rice and {Van Der Lee}, {Sven J.} and {De Jager}, {Philip L.} and Geschwind, {Daniel H.} and Matthias Riemenschneider and Steffi Riedel-Heller and Rotter, {Jerome I.} and Gerhard Ransmayr and Hyman, {Bradley T.} and Carlos Cruchaga and Montserrat Alegret and Bendik Winsvold and Priit Palta and Farh, {Kai How} and Ester Cuenca-Leon and Nicholas Furlotte and Tobias Kurth and Lannie Ligthart and Terwindt, {Gisela M.} and Tobias Freilinger and Caroline Ran and Gordon, {Scott D.} and Guntram Borck and Adams, {Hieab H.H.} and Terho Lehtim{\"a}ki and Juho Wedenoja and Buring, {Julie E.} and Markus Sch{\"u}rks and Maria Hrafnsdottir and Hottenga, {Jouke Jan} and Brenda Penninx and Ville Artto and Mari Kaunisto and Salli Veps{\"a}l{\"a}inen and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Kurki, {Mitja I.} and Eija H{\"a}m{\"a}l{\"a}inen and Hailiang Huang and Jie Huang and Cynthia Sandor and Caleb Webber and Bertram Muller-Myhsok and Stefan Schreiber and Veikko Salomaa and Elizabeth Loehrer and Hartmut G{\"o}bel and Alfons Macaya and Patricia Pozo-Rosich and Thomas Hansen and Thomas Werge and Jaakko Kaprio and Andres Metspalu and Christian Kubisch and Ferrari, {Michel D.} and Belin, {Andrea C.} and {Van Den Maagdenberg}, {Arn M.J.M.} and Zwart, {John Anker} and Dorret Boomsma and Nicholas Eriksson and Jes Olesen and Chasman, {Daniel I.} and Nyholt, {Dale R.} and Andreja Avbersek and Larry Baum and Samuel Berkovic and Jonathan Bradfield and Russell Buono and Catarino, {Claudia B.} and Patrick Cossette and {De Jonghe}, Peter and Chantal Depondt and Dennis Dlugos and Ferraro, {Thomas N.} and Jacqueline French and Helle Hjalgrim and Jennifer Jamnadas-Khoda and Reetta K{\"a}lvi{\"a}inen and Kunz, {Wolfram S.} and Holger Lerche and Costin Leu and Dick Lindhout and Warren Lo and Daniel Lowenstein and Mark McCormack and M{\o}ller, {Rikke S.} and Anne Molloy and Ng, {Ping Wing} and Karen Oliver and Michael Privitera and Rodney Radtke and Ruppert, {Ann Kathrin} and Thomas Sander and Steven Schachter and Christoph Schankin and Ingrid Scheffer and Susanne Schoch and Sisodiya, {Sanjay M.} and Philip Smith and Michael Sperling and Pasquale Striano and Rainer Surges and {Neil Thomas}, G. and Frank Visscher and Whelan, {Christopher D.} and Federico Zara and Heinzen, {Erin L.} and Anthony Marson and Felicitas Becker and Hans Stroink and Fritz Zimprich and Thomas Gasser and Raphael Gibbs and Peter Heutink and Maria Martinez and Morris, {Huw R.} and Manu Sharma and Mina Ryten and Mok, {Kin Y.} and Sara Pulit and Steve Bevan and Elizabeth Holliday and John Attia and Thomas Battey and Giorgio Boncoraglio and Vincent Thijs and Chen, {Wei Min} and Braxton Mitchell and Peter Rothwell and Pankaj Sharma and Cathie Sudlow and Astrid Vicente and Hugh Markus and Christina Kourkoulis and Joana Pera and Miriam Raffeld and Scott Silliman and Perica, {Vesna Boraska} and Thornton, {Laura M.} and Huckins, {Laura M.} and {William Rayner}, N. and Lewis, {Cathryn M.} and Monica Gratacos and Filip Rybakowski and Anna Keski-Rahkonen and Anu Raevuori and Hudson, {James I.} and Ted Reichborn-Kjennerud and Palmiero Monteleone and Andreas Karwautz and Katrin Mannik and Baker, {Jessica H.} and O'Toole, {Julie K.} and Trace, {Sara E.} and Davis, {Oliver S.P.} and Helder, {Sietske G.} and Stefan Ehrlich and Beate Herpertz-Dahlmann and Danner, {Unna N.} and {Van Elburg}, {Annemarie A.} and Maurizio Clementi and Monica Forzan and Elisa Docampo and Jolanta Lissowska and Joanna Hauser and Alfonso Tortorella and Sarah Cohen-Woods",

year = "2018",

month = jun,

day = "22",

doi = "10.1126/science.aap8757",

language = "English",

volume = "360",

journal = "Science",

issn = "0036-8075",

publisher = "PubMed",

number = "6395",

}

TY - JOUR

T1 - Analysis of shared heritability in common disorders of the brain

AU - The Brainstorm Consortium

AU - Anttila, Verneri

AU - Bulik-Sullivan, Brendan

AU - Finucane, Hilary K.

AU - Walters, Raymond K.

AU - Bras, Jose

AU - Duncan, Laramie

AU - Escott-Price, Valentina

AU - Falcone, Guido J.

AU - Gormley, Padhraig

AU - Malik, Rainer

AU - Patsopoulos, Nikolaos A.

AU - Ripke, Stephan

AU - Wei, Zhi

AU - Yu, Dongmei

AU - Lee, Phil H.

AU - Turley, Patrick

AU - Grenier-Boley, Benjamin

AU - Chouraki, Vincent

AU - Kamatani, Yoichiro

AU - Berr, Claudine

AU - Letenneur, Luc

AU - Hannequin, Didier

AU - Amouyel, Philippe

AU - Boland, Anne

AU - Deleuze, Jean François

AU - Duron, Emmanuelle

AU - Vardarajan, Badri N.

AU - Reitz, Christiane

AU - Goate, Alison M.

AU - Huentelman, Matthew J.

AU - Ilyas Kamboh, M.

AU - Larson, Eric B.

AU - Rogaeva, Ekaterina

AU - George-Hyslop, Peter St

AU - Hakonarson, Hakon

AU - Kukull, Walter A.

AU - Farrer, Lindsay A.

AU - Barnes, Lisa L.

AU - Beach, Thomas G.

AU - Yesim Demirci, F.

AU - Head, Elizabeth

AU - Hulette, Christine M.

AU - Jicha, Gregory A.

AU - Kauwe, John S.K.

AU - Kaye, Jeffrey A.

AU - Leverenz, James B.

AU - Levey, Allan I.

AU - Lieberman, Andrew P.

AU - Pankratz, Vernon S.

AU - Poon, Wayne W.

AU - Quinn, Joseph F.

AU - Saykin, Andrew J.

AU - Schneider, Lon S.

AU - Smith, Amanda G.

AU - Sonnen, Joshua A.

AU - Stern, Robert A.

AU - Van Deerlin, Vivianna M.

AU - Van Eldik, Linda J.

AU - Harold, Denise

AU - Russo, Giancarlo

AU - Rubinsztein, David C.

AU - Bayer, Anthony

AU - Tsolaki, Magda

AU - Proitsi, Petra

AU - Fox, Nick C.

AU - Hampel, Harald

AU - Owen, Michael J.

AU - Mead, Simon

AU - Passmore, Peter

AU - Morgan, Kevin

AU - Nöthen, Markus M.

AU - Schott, Jonathan M.

AU - Rossor, Martin

AU - Lupton, Michelle K.

AU - Hoffmann, Per

AU - Kornhuber, Johannes

AU - Lawlor, Brian

AU - McQuillin, Andrew

AU - Al-Chalabi, Ammar

AU - Bis, Joshua C.

AU - Ruiz, Agustin

AU - Boada, Mercè

AU - Seshadri, Sudha

AU - Beiser, Alexa

AU - Rice, Kenneth

AU - Van Der Lee, Sven J.

AU - De Jager, Philip L.

AU - Geschwind, Daniel H.

AU - Riemenschneider, Matthias

AU - Riedel-Heller, Steffi

AU - Rotter, Jerome I.

AU - Ransmayr, Gerhard

AU - Hyman, Bradley T.

AU - Cruchaga, Carlos

AU - Alegret, Montserrat

AU - Winsvold, Bendik

AU - Palta, Priit

AU - Farh, Kai How

AU - Cuenca-Leon, Ester

AU - Furlotte, Nicholas

AU - Kurth, Tobias

AU - Ligthart, Lannie

AU - Terwindt, Gisela M.

AU - Freilinger, Tobias

AU - Ran, Caroline

AU - Gordon, Scott D.

AU - Borck, Guntram

AU - Adams, Hieab H.H.

AU - Lehtimäki, Terho

AU - Wedenoja, Juho

AU - Buring, Julie E.

AU - Schürks, Markus

AU - Hrafnsdottir, Maria

AU - Hottenga, Jouke Jan

AU - Penninx, Brenda

AU - Artto, Ville

AU - Kaunisto, Mari

AU - Vepsäläinen, Salli

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Kurki, Mitja I.

AU - Hämäläinen, Eija

AU - Huang, Hailiang

AU - Huang, Jie

AU - Sandor, Cynthia

AU - Webber, Caleb

AU - Muller-Myhsok, Bertram

AU - Schreiber, Stefan

AU - Salomaa, Veikko

AU - Loehrer, Elizabeth

AU - Göbel, Hartmut

AU - Macaya, Alfons

AU - Pozo-Rosich, Patricia

AU - Hansen, Thomas

AU - Werge, Thomas

AU - Kaprio, Jaakko

AU - Metspalu, Andres

AU - Kubisch, Christian

AU - Ferrari, Michel D.

AU - Belin, Andrea C.

AU - Van Den Maagdenberg, Arn M.J.M.

AU - Zwart, John Anker

AU - Boomsma, Dorret

AU - Eriksson, Nicholas

AU - Olesen, Jes

AU - Chasman, Daniel I.

AU - Nyholt, Dale R.

AU - Avbersek, Andreja

AU - Baum, Larry

AU - Berkovic, Samuel

AU - Bradfield, Jonathan

AU - Buono, Russell

AU - Catarino, Claudia B.

AU - Cossette, Patrick

AU - De Jonghe, Peter

AU - Depondt, Chantal

AU - Dlugos, Dennis

AU - Ferraro, Thomas N.

AU - French, Jacqueline

AU - Hjalgrim, Helle

AU - Jamnadas-Khoda, Jennifer

AU - Kälviäinen, Reetta

AU - Kunz, Wolfram S.

AU - Lerche, Holger

AU - Leu, Costin

AU - Lindhout, Dick

AU - Lo, Warren

AU - Lowenstein, Daniel

AU - McCormack, Mark

AU - Møller, Rikke S.

AU - Molloy, Anne

AU - Ng, Ping Wing

AU - Oliver, Karen

AU - Privitera, Michael

AU - Radtke, Rodney

AU - Ruppert, Ann Kathrin

AU - Sander, Thomas

AU - Schachter, Steven

AU - Schankin, Christoph

AU - Scheffer, Ingrid

AU - Schoch, Susanne

AU - Sisodiya, Sanjay M.

AU - Smith, Philip

AU - Sperling, Michael

AU - Striano, Pasquale

AU - Surges, Rainer

AU - Neil Thomas, G.

AU - Visscher, Frank

AU - Whelan, Christopher D.

AU - Zara, Federico

AU - Heinzen, Erin L.

AU - Marson, Anthony

AU - Becker, Felicitas

AU - Stroink, Hans

AU - Zimprich, Fritz

AU - Gasser, Thomas

AU - Gibbs, Raphael

AU - Heutink, Peter

AU - Martinez, Maria

AU - Morris, Huw R.

AU - Sharma, Manu

AU - Ryten, Mina

AU - Mok, Kin Y.

AU - Pulit, Sara

AU - Bevan, Steve

AU - Holliday, Elizabeth

AU - Attia, John

AU - Battey, Thomas

AU - Boncoraglio, Giorgio

AU - Thijs, Vincent

AU - Chen, Wei Min

AU - Mitchell, Braxton

AU - Rothwell, Peter

AU - Sharma, Pankaj

AU - Sudlow, Cathie

AU - Vicente, Astrid

AU - Markus, Hugh

AU - Kourkoulis, Christina

AU - Pera, Joana

AU - Raffeld, Miriam

AU - Silliman, Scott

AU - Perica, Vesna Boraska

AU - Thornton, Laura M.

AU - Huckins, Laura M.

AU - William Rayner, N.

AU - Lewis, Cathryn M.

AU - Gratacos, Monica

AU - Rybakowski, Filip

AU - Keski-Rahkonen, Anna

AU - Raevuori, Anu

AU - Hudson, James I.

AU - Reichborn-Kjennerud, Ted

AU - Monteleone, Palmiero

AU - Karwautz, Andreas

AU - Mannik, Katrin

AU - Baker, Jessica H.

AU - O'Toole, Julie K.

AU - Trace, Sara E.

AU - Davis, Oliver S.P.

AU - Helder, Sietske G.

AU - Ehrlich, Stefan

AU - Herpertz-Dahlmann, Beate

AU - Danner, Unna N.

AU - Van Elburg, Annemarie A.

AU - Clementi, Maurizio

AU - Forzan, Monica

AU - Docampo, Elisa

AU - Lissowska, Jolanta

AU - Hauser, Joanna

AU - Tortorella, Alfonso

AU - Cohen-Woods, Sarah

PY - 2018/6/22

Y1 - 2018/6/22

N2 - Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

AB - Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

KW - Brain disorders

KW - genetic risks

KW - genomics

KW - comorbidity

UR - http://www.scopus.com/inward/record.url?scp=85049284114&partnerID=8YFLogxK

U2 - 10.1126/science.aap8757

DO - 10.1126/science.aap8757

M3 - Article

C2 - 29930110

AN - SCOPUS:85049284114

SN - 0036-8075

VL - 360

JO - Science

JF - Science

IS - 6395

M1 - eaap8757

ER -

Analysis of shared heritability in common disorders of the brain

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Keywords

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