Identification of common genetic risk variants for autism spectrum disorder.
Adolescent
Autism Spectrum Disorder
/ genetics
Case-Control Studies
Child
Child, Preschool
Denmark
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
/ methods
Humans
Male
Multifactorial Inheritance
/ genetics
Phenotype
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
24
11
2017
accepted:
12
12
2018
pubmed:
26
2
2019
medline:
25
4
2019
entrez:
27
2
2019
Statut:
ppublish
Résumé
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
Identifiants
pubmed: 30804558
doi: 10.1038/s41588-019-0344-8
pii: 10.1038/s41588-019-0344-8
pmc: PMC6454898
mid: NIHMS1015648
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
431-444Subventions
Organisme : NIMH NIH HHS
ID : R01 MH097849
Pays : United States
Organisme : NIMH NIH HHS
ID : R00 MH113823
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIH HHS
ID : S10 OD018164
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH094432
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113362
Pays : United States
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0200243
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : K01 DK114379
Pays : United States
Organisme : NIMH NIH HHS
ID : R56 MH097849
Pays : United States
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH111661
Pays : United States
Investigateurs
Naomi R Wray
(NR)
Maciej Trzaskowski
(M)
Enda M Byrne
(EM)
Abdel Abdellaoui
(A)
Mark J Adams
(MJ)
Tracy M Air
(TM)
Till F M Andlauer
(TFM)
Silviu-Alin Bacanu
(SA)
Aartjan T F Beekman
(ATF)
Tim B Bigdeli
(TB)
Elisabeth B Binder
(EB)
Douglas H R Blackwood
(DHR)
Julien Bryois
(J)
Henriette N Buttenschøn
(HN)
Na Cai
(N)
Enrique Castelao
(E)
Toni-Kim Clarke
(TK)
Jonathan R I Coleman
(JRI)
Lucía Colodro-Conde
(L)
Baptiste Couvy-Duchesne
(B)
Nick Craddock
(N)
Gregory E Crawford
(GE)
Gail Davies
(G)
Ian J Deary
(IJ)
Franziska Degenhardt
(F)
Eske M Derks
(EM)
Nese Direk
(N)
Conor V Dolan
(CV)
Erin C Dunn
(EC)
Thalia C Eley
(TC)
Valentina Escott-Price
(V)
Farnush Farhadi Hassan Kiadeh
(FFH)
Hilary K Finucane
(HK)
Andreas J Forstner
(AJ)
Josef Frank
(J)
Héléna A Gaspar
(HA)
Michael Gill
(M)
Fernando S Goes
(FS)
Scott D Gordon
(SD)
Lynsey S Hall
(LS)
Thomas F Hansen
(TF)
Stefan Herms
(S)
Ian B Hickie
(IB)
Per Hoffmann
(P)
Georg Homuth
(G)
Carsten Horn
(C)
Jouke-Jan Hottenga
(JJ)
Marcus Ising
(M)
Rick Jansen
(R)
Eric Jorgenson
(E)
James A Knowles
(JA)
Isaac S Kohane
(IS)
Julia Kraft
(J)
Warren W Kretzschmar
(WW)
Jesper Krogh
(J)
Zoltán Kutalik
(Z)
Yihan Li
(Y)
Penelope A Lind
(PA)
Donald J MacIntyre
(DJ)
Dean F MacKinnon
(DF)
Robert M Maier
(RM)
Wolfgang Maier
(W)
Jonathan Marchini
(J)
Hamdi Mbarek
(H)
Patrick McGrath
(P)
Peter McGuffin
(P)
Sarah E Medland
(SE)
Divya Mehta
(D)
Christel M Middeldorp
(CM)
Evelin Mihailov
(E)
Yuri Milaneschi
(Y)
Lili Milani
(L)
Francis M Mondimore
(FM)
Grant W Montgomery
(GW)
Sara Mostafavi
(S)
Niamh Mullins
(N)
Matthias Nauck
(M)
Bernard Ng
(B)
Michel G Nivard
(MG)
Dale R Nyholt
(DR)
Paul F O'Reilly
(PF)
Hogni Oskarsson
(H)
Michael J Owen
(MJ)
Jodie N Painter
(JN)
Roseann E Peterson
(RE)
Erik Pettersson
(E)
Wouter J Peyrot
(WJ)
Giorgio Pistis
(G)
Danielle Posthuma
(D)
Jorge A Quiroz
(JA)
John P Rice
(JP)
Brien P Riley
(BP)
Margarita Rivera
(M)
Saira Saeed Mirza
(SS)
Robert Schoevers
(R)
Eva C Schulte
(EC)
Ling Shen
(L)
Jianxin Shi
(J)
Stanley I Shyn
(SI)
Engilbert Sigurdsson
(E)
Grant C B Sinnamon
(GCB)
Johannes H Smit
(JH)
Daniel J Smith
(DJ)
Fabian Streit
(F)
Jana Strohmaier
(J)
Katherine E Tansey
(KE)
Henning Teismann
(H)
Alexander Teumer
(A)
Wesley Thompson
(W)
Pippa A Thomson
(PA)
Thorgeir E Thorgeirsson
(TE)
Matthew Traylor
(M)
Jens Treutlein
(J)
Vassily Trubetskoy
(V)
André G Uitterlinden
(AG)
Daniel Umbricht
(D)
Sandra Van der Auwera
(S)
Albert M van Hemert
(AM)
Alexander Viktorin
(A)
Peter M Visscher
(PM)
Yunpeng Wang
(Y)
Bradley T Webb
(BT)
Shantel Marie Weinsheimer
(SM)
Jürgen Wellmann
(J)
Gonneke Willemsen
(G)
Stephanie H Witt
(SH)
Yang Wu
(Y)
Hualin S Xi
(HS)
Jian Yang
(J)
Futao Zhang
(F)
Volker Arolt
(V)
Bernhard T Baune
(BT)
Klaus Berger
(K)
Dorret I Boomsma
(DI)
Sven Cichon
(S)
Udo Dannlowski
(U)
E J C de Geus
(EJC)
J Raymond DePaulo
(JR)
Enrico Domenici
(E)
Katharina Domschke
(K)
Tõnu Esko
(T)
Hans J Grabe
(HJ)
Steven P Hamilton
(SP)
Caroline Hayward
(C)
Andrew C Heath
(AC)
Kenneth S Kendler
(KS)
Stefan Kloiber
(S)
Glyn Lewis
(G)
Qingqin S Li
(QS)
Susanne Lucae
(S)
Pamela A F Madden
(PAF)
Patrik K Magnusson
(PK)
Nicholas G Martin
(NG)
Andrew M McIntosh
(AM)
Andres Metspalu
(A)
Bertram Müller-Myhsok
(B)
Markus M Nöthen
(MM)
Michael C O'Donovan
(MC)
Sara A Paciga
(SA)
Nancy L Pedersen
(NL)
Brenda W J H Penninx
(BWJH)
Roy H Perlis
(RH)
David J Porteous
(DJ)
James B Potash
(JB)
Martin Preisig
(M)
Marcella Rietschel
(M)
Catherine Schaefer
(C)
Thomas G Schulze
(TG)
Jordan W Smoller
(JW)
Henning Tiemeier
(H)
Rudolf Uher
(R)
Henry Völzke
(H)
Myrna M Weissman
(MM)
Cathryn M Lewis
(CM)
Douglas F Levinson
(DF)
Gerome Breen
(G)
Michelle Agee
(M)
Babak Alipanahi
(B)
Adam Auton
(A)
Robert K Bell
(RK)
Katarzyna Bryc
(K)
Sarah L Elson
(SL)
Pierre Fontanillas
(P)
Nicholas A Furlotte
(NA)
Bethann S Hromatka
(BS)
Karen E Huber
(KE)
Aaron Kleinman
(A)
Nadia K Litterman
(NK)
Matthew H McIntyre
(MH)
Joanna L Mountain
(JL)
Elizabeth S Noblin
(ES)
Carrie A M Northover
(CAM)
Steven J Pitts
(SJ)
J Fah Sathirapongsasuti
(JF)
Olga V Sazonova
(OV)
Janie F Shelton
(JF)
Suyash Shringarpure
(S)
Joyce Y Tung
(JY)
Vladimir Vacic
(V)
Catherine H Wilson
(CH)
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