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Analysis of shared heritability in common disorders of the brain

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J.; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A.; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H.; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N.; Reitz, Christiane; Goate, Alison M.; Huentelman, Matthew J.; Kamboh, M. Ilyas; Larson, Eric B.; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A.; Farrer, Lindsay A.; Barnes, Lisa L.; Beach, Thomas G.; Demirci, F. Yesim; Head, Elizabeth; Hulette, Christine M.; Jicha, Gregory A.; Kauwe, John S.K.; Kaye, Jeffrey A.; Leverenz, James B.; Levey, Allan I.; Lieberman, Andrew P.; Pankratz, Vernon S.; Poon, Wayne W.; Quinn, Joseph F.; Saykin, Andrew J.; Schneider, Lon S.;...

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Authors

Verneri Anttila

Brendan Bulik-Sullivan

Hilary K. Finucane

Raymond K. Walters

Jose Bras

Laramie Duncan

Valentina Escott-Price

Guido J. Falcone

Padhraig Gormley

Rainer Malik

Nikolaos A. Patsopoulos

Stephan Ripke

Zhi Wei

Dongmei Yu

Phil H. Lee

Patrick Turley

Benjamin Grenier-Boley

Vincent Chouraki

Yoichiro Kamatani

Claudine Berr

Luc Letenneur

Didier Hannequin

Philippe Amouyel

Anne Boland

Jean-François Deleuze

Emmanuelle Duron

Badri N. Vardarajan

Christiane Reitz

Alison M. Goate

Matthew J. Huentelman

M. Ilyas Kamboh

Eric B. Larson

Ekaterina Rogaeva

Peter St George-Hyslop

Hakon Hakonarson

Walter A. Kukull

Lindsay A. Farrer

Lisa L. Barnes

Thomas G. Beach

F. Yesim Demirci

Elizabeth Head

Christine M. Hulette

Gregory A. Jicha

John S.K. Kauwe

Jeffrey A. Kaye

James B. Leverenz

Allan I. Levey

Andrew P. Lieberman

Vernon S. Pankratz

Wayne W. Poon

Joseph F. Quinn

Andrew J. Saykin

Lon S. Schneider

Amanda G. Smith

Joshua A. Sonnen

Robert A. Stern

Vivianna M. Van Deerlin

Linda J. Van Eldik

Denise Harold

Giancarlo Russo

David C. Rubinsztein

Anthony Bayer

Magda Tsolaki

Petra Proitsi

Nick C. Fox

Harald Hampel

Michael J. Owen

Simon Mead

Peter Passmore

Kevin Morgan

Markus M. Nöthen

Martin Rossor

Michelle K. Lupton

Per Hoffmann

Johannes Kornhuber

Brian Lawlor

Andrew McQuillin

Ammar Al-Chalabi

Joshua C Bis

Agustin Ruiz

Mercè Boada

Sudha Seshadri

Alexa Beiser

Kenneth Rice

Sven J. van der Lee

Philip L. De Jager

Daniel H. Geschwind

Matthias Riemenschneider

Steffi Riedel-Heller

Jerome I Rotter

Gerhard Ransmayr

Bradley T. Hyman

Carlos Cruchaga

Montserrat Alegret

Bendik Winsvold

Priit Palta

Kai-How Farh

Ester Cuenca-Leon

Nicholas Furlotte

Tobias Kurth

Lannie Ligthart

Gisela M. Terwindt

Tobias Freilinger

Caroline Ran

Scott D. Gordon

Guntram Borck

Hieab H.H. Adams

Terho Lehtimäki

Juho Wedenoja

Julie E. Buring

Markus Schürks

Maria Hrafnsdottir

Jouke-Jan Hottenga

Brenda Penninx

Ville Artto

Mari Kaunisto

Salli Vepsäläinen

Nicholas G. Martin

Grant W. Montgomery

Mitja I. Kurki

Eija Hämäläinen

Hailiang Huang

Jie Huang

Cynthia Sandor

Caleb Webber

Bertram Muller-Myhsok

Stefan Schreiber

Veikko Salomaa

Elizabeth Loehrer

Hartmut Göbel

Alfons Macaya

Patricia Pozo-Rosich

Thomas Hansen

Thomas Werge

Jaakko Kaprio

Andres Metspalu

Christian Kubisch

Michel D. Ferrari

Andrea C. Belin

Arn M.J.M. van den Maagdenberg

John-Anker Zwart

Dorret Boomsma

Nicholas Eriksson

Jes Olesen

Daniel I. Chasman

Dale R. Nyholt

Andreja Avbersek

Larry Baum

Samuel Berkovic

Jonathan Bradfield

Russell Buono

Claudia B. Catarino

Patrick Cossette

Peter De Jonghe

Chantal Depondt

Dennis Dlugos

Thomas N. Ferraro

Jacqueline French

Helle Hjalgrim

Jennifer Jamnadas-Khoda

Reetta Kälviäinen

Wolfram S. Kunz

Holger Lerche

Costin Leu

Dick Lindhout

Warren Lo

Daniel Lowenstein

Mark McCormack

Rikke S. Møller

Anne Molloy

Ping-Wing Ng

Karen Oliver

Michael Privitera

Rodney Radtke

Ann-Kathrin Ruppert

Thomas Sander

Steven Schachter

Christoph Schankin

Ingrid Scheffer

Susanne Schoch

Sanjay M. Sisodiya

Philip Smith

Michael Sperling

Pasquale Striano

Rainer Surges

G. Neil Thomas

Frank Visscher

Christopher D. Whelan

Federico Zara

Erin L. Heinzen

Anthony Marson

Felicitas Becker

Hans Stroink

Fritz Zimprich

Thomas Gasser

Raphael Gibbs

Peter Heutink

Maria Martinez

Huw R. Morris

Manu Sharma

Mina Ryten

Kin Y. Mok

Sara Pulit

Steve Bevan

Elizabeth Holliday

John Attia

Thomas Battey

Giorgio Boncoraglio

Vincent Thijs

Wei-Min Chen

Braxton Mitchell

Peter Rothwell

Pankaj Sharma

Cathie Sudlow

Astrid Vicente

Hugh Markus

Christina Kourkoulis

Joana Pera

Miriam Raffeld

Scott Silliman

Vesna Boraska Perica

Laura M. Thornton

Laura M. Huckins

N. William Rayner

Cathryn M. Lewis

Monica Gratacos

Filip Rybakowski

Anna Keski-Rahkonen

Anu Raevuori

James I. Hudson

Ted Reichborn-Kjennerud

Palmiero Monteleone

Andreas Karwautz

Katrin Mannik

Jessica H. Baker

Julie K. O’Toole

Sara E. Trace

Oliver S. P. Davis

Sietske G. Helder

Stefan Ehrlich

Beate Herpertz-Dahlmann

Unna N. Danner

Annemarie A. van Elburg

Maurizio Clementi

Monica Forzan

Elisa Docampo

Jolanta Lissowska

Joanna Hauser

Alfonso Tortorella

Mario Maj

Fragiskos Gonidakis

Konstantinos Tziouvas

Hana Papezova

Zeynep Yilmaz

Gudrun Wagner

Sarah Cohen-Woods

Stefan Herms

Antonio Julià

Raquel Rabionet

Danielle M. Dick

Samuli Ripatti

Ole A. Andreassen

Thomas Espeseth

Astri J. Lundervold

Vidar M. Steen

Dalila Pinto

Stephen W. Scherer

Harald Aschauer

Alexandra Schosser

Lars Alfredsson

Leonid Padyukov

Katherine A. Halmi

James Mitchell

Michael Strober

Andrew W. Bergen

Walter Kaye

Jin Peng Szatkiewicz

Bru Cormand

Josep Antoni Ramos-Quiroga

Cristina Sánchez-Mora

Marta Ribasés

Miguel Casas

Amaia Hervas

Maria Jesús Arranz

Jan Haavik

Tetyana Zayats

Stefan Johansson

Nigel Williams

Astrid Dempfle

Aribert Rothenberger

Jonna Kuntsi

Robert D. Oades

Tobias Banaschewski

Barbara Franke

Jan K. Buitelaar

Alejandro Arias Vasquez

Alysa E. Doyle

Andreas Reif

Klaus-Peter Lesch

Christine Freitag

Olga Rivero

Haukur Palmason

Marcel Romanos

Kate Langley

Marcella Rietschel

Stephanie H. Witt

Soeren Dalsgaard

Anders D. Børglum

Irwin Waldman

Beth Wilmot

Nikolas Molly

Claiton H.D. Bau

Jennifer Crosbie

Russell Schachar

Sandra K. Loo

James J. McGough

Eugenio H. Grevet

Sarah E. Medland

Elise Robinson

Lauren A. Weiss

Elena Bacchelli

Anthony Bailey

Vanessa Bal

Agatino Battaglia

Catalina Betancur

Patrick Bolton

Rita Cantor

Patrícia Celestino-Soper

Geraldine Dawson

Silvia De Rubeis

Frederico Duque

Andrew Green

Sabine M. Klauck

Marion Leboyer

Pat Levitt

Elena Maestrini

Shrikant Mane

Daniel Moreno- De-Luca

Jeremy Parr

Regina Regan

Abraham Reichenberg

Sven Sandin

Jacob Vorstman

Thomas Wassink

Ellen Wijsman

Edwin Cook

Susan Santangelo

Richard Delorme

Bernadette Rogé

Tiago Magalhaes

Dan Arking

Thomas G. Schulze

Robert C. Thompson

Jana Strohmaier

Keith Matthews

Ingrid Melle

Derek Morris

Douglas Blackwood

Andrew McIntosh

Sarah E Bergen

Martin Schalling

Stéphane Jamain

Anna Maaser

Sascha B. Fischer

Céline S. Reinbold

Janice M. Fullerton

José Guzman-Parra

Fermin Mayoral

Peter R. Schofield

Sven Cichon

Thomas W. Mühleisen

Franziska Degenhardt

Johannes Schumacher

Michael Bauer

Philip B. Mitchell

Elliot S. Gershon

John Rice

James B. Potash

Peter P. Zandi

Nick Craddock

I. Nicol Ferrier

Martin Alda

Guy A. Rouleau

Gustavo Turecki

Roel Ophoff

Carlos Pato

Adebayo Anjorin

Eli Stahl

Markus Leber

Piotr M. Czerski

Cristiana Cruceanu

Ian R. Jones

Danielle Posthuma

Till F.M. Andlauer

Andreas J. Forstner

Fabian Streit

Bernhard T. Baune

Tracy Air

Grant Sinnamon

Naomi R. Wray

Donald J. MacIntyre

David Porteous

Georg Homuth

Margarita Rivera

Jakob Grove

Christel M. Middeldorp

Ian Hickie

Michele Pergadia

Divya Mehta

Johannes H. Smit

Rick Jansen

Eco de Geus

Erin Dunn

Qingqin S. Li

Matthias Nauck

Robert A. Schoevers

Aartjan TF Beekman

James A. Knowles

Alexander Viktorin

Paul Arnold

Cathy L. Barr

Gabriel Bedoya-Berrio

O. Joseph Bienvenu

Helena Brentani

Christie Burton

Beatriz Camarena

Carolina Cappi

Danielle Cath

Maria Cavallini

Daniele Cusi

Sabrina Darrow

Damiaan Denys

Eske M. Derks

Andrea Dietrich

Thomas Fernandez

Martijn Figee

Nelson Freimer

Gloria Gerber

Marco Grados

Erica Greenberg

Gregory L. Hanna

Andreas Hartmann

Matthew E. Hirschtritt

Pieter J. Hoekstra

Alden Huang

Chaim Huyser

Cornelia Illmann

Michael Jenike

Samuel Kuperman

Bennett Leventhal

Christine Lochner

Gholson J. Lyon

Fabio Macciardi

Marcos Madruga-Garrido

Irene A. Malaty

Athanasios Maras

Lauren McGrath

Eurípedes C. Miguel

Pablo Mir

Gerald Nestadt

Humberto Nicolini

Michael S. Okun

Andrew Pakstis

Peristera Paschou

John Piacentini

Christopher Pittenger

Kerstin Plessen

Vasily Ramensky

Eliana M. Ramos

Victor Reus

Margaret A. Richter

Mark A. Riddle

Mary M. Robertson

Veit Roessner

Maria Rosário

Jack F. Samuels

Paul Sandor

Dan J. Stein

Fotis Tsetsos

Filip Van Nieuwerburgh

Sarah Weatherall

Jens R. Wendland

Tomasz Wolanczyk

Yulia Worbe

Gwyneth Zai

Fernando S. Goes

Nicole McLaughlin

Paul S. Nestadt

Hans-Jorgen Grabe

Christel Depienne

Anuar Konkashbaev

Nuria Lanzagorta

Ana Valencia-Duarte

Elvira Bramon

Nancy Buccola

Wiepke Cahn

Murray Cairns

Siow A. Chong

David Cohen

Benedicto Crespo-Facorro

James Crowley

Michael Davidson

Lynn DeLisi

Timothy Dinan

Gary Donohoe

Elodie Drapeau

Jubao Duan

Lieuwe Haan

David Hougaard

Sena Karachanak-Yankova

Andrey Khrunin

Janis Klovins

Vaidutis Kučinskas

Jimmy Lee Chee Keong

Svetlana Limborska

Carmel Loughland

Jouko Lönnqvist

Brion Maher

Manuel Mattheisen

Colm McDonald

Kieran C. Murphy

Igor Nenadic

Jim van Os

Christos Pantelis

Michele Pato

Tracey Petryshen

Digby Quested

Panos Roussos

Alan R. Sanders

Ulrich Schall

Sibylle G. Schwab

Kang Sim

Hon-Cheong So

Elisabeth Stögmann

Mythily Subramaniam

Draga Toncheva

John Waddington

James Walters

Mark Weiser

Wei Cheng

Robert Cloninger

David Curtis

Pablo V. Gejman

Frans Henskens

Morten Mattingsdal

Sang-Yun Oh

Rodney Scott

Bradley Webb

Gerome Breen

Claire Churchhouse

Cynthia M. Bulik

Mark Daly

Martin Dichgans

Stephen V. Faraone

Rita Guerreiro

Peter Holmans

Kenneth S. Kendler

Bobby Koeleman

Carol A. Mathews

Alkes Price

Jeremiah Scharf

Pamela Sklar

Julie Williams

Nicholas W. Wood

Chris Cotsapas

Aarno Palotie

Jordan W. Smoller

Patrick Sullivan

Jonathan Rosand

Aiden Corvin

Benjamin M. Neale



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.

Citation

Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., …Neale, B. M. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), Article eaap8757. https://doi.org/10.1126/science.aap8757

Journal Article Type Article
Acceptance Date Apr 24, 2018
Online Publication Date Jun 22, 2018
Publication Date Jun 22, 2018
Deposit Date Jul 2, 2018
Publicly Available Date Mar 28, 2024
Journal Science
Print ISSN 0036-8075
Electronic ISSN 1095-9203
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 360
Issue 6395
Article Number eaap8757
DOI https://doi.org/10.1126/science.aap8757
Public URL https://nottingham-repository.worktribe.com/output/940279
Publisher URL http://dx.doi.org/10.1126/science.aap8757

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