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A genome-wide scan for common alleles affecting risk for autism

Authors :
Veronica J. Vieland
Stephen W. Scherer
Elizabeth A. Heron
Barbara Parrini
Jeremy R. Parr
Louise Gallagher
Jeff Munson
Annemarie Poustka
Susan E. Folstein
Irene Drmic
Gudrun Nygren
John P. Rice
Jeff Salt
Simon Wallace
Geraldine Dawson
Daniel H. Geschwind
Annette Estes
Sean Brennan
Alistair T. Pagnamenta
Nancy J. Minshew
Christina Corsello
Jonathan Green
William M. McMahon
Christopher Gillberg
Kathryn Roeder
Lambertus Klei
Anath C. Lionel
Bridget A. Fernandez
Thomas Bourgeron
Ellen M. Wijsman
Gerard D. Schellenberg
Wendy Roberts
Jeremy Goldberg
Frederico Duque
Ghazala Mirza
Sean Ennis
Joana Almeida
Nadine M. Melhem
Jillian P. Casey
Roberta Igliozzi
Ricardo Segurado
Carine Mantoulan
Katy Renshaw
Kai Wang
Andrew D. Paterson
Raffaella Tancredi
Matthew Nicholas Hill
Richard Anney
Christian R. Marshall
Anthony P. Monaco
Linda Lotspeich
Marion Leboyer
Richard Holt
Andrew Pickles
Vlad Kustanovich
William M. Mahoney
Jessica Brian
Inês Sousa
Peter Szatmari
Vanessa Hus
Janine A. Lamb
Hakon Hakonarson
Lonnie Zwaigenbaum
John Tsiantis
David J. Posey
Olena Korvatska
Guillermo Casallo
Rita M. Cantor
Bhooma Thiruvahindrapduram
Nadia Bolshakova
Sven Bölte
Alison K. Merikangas
Brian L. Yaspan
Cecilia Kim
Andrew Crossett
Fritz Poustka
Danielle Zurawiecki
Agatino Battaglia
Sabata C. Lund
Ann P. Thompson
Bennett L. Leventhal
Jessica Rickaby
Zhouzhi Wang
John I. Nurnberger
Astrid M. Vicente
Maretha de Jonge
Tiago R. Magalhaes
Michael L. Cuccaro
Val C. Sheffield
Nuala Sykes
Elena Maestrini
Guiomar Oliveira
Joseph D. Buxbaum
Fred R. Volkmar
Shawn Wood
Magdalena Laskawiec
Katherine Sansom
Herman van Engeland
Jane McGrath
Thomas H. Wassink
Su H. Chu
Elena Bacchelli
Carolyn Noakes
Ann Le Couteur
Catarina Correia
Ohsuke Migita
Bernie Devlin
Hilary Coon
Gillian Baird
Joseph Piven
Tom Berney
Ana Tryfon
Abdul Noor
Patrick Bolton
Latha Soorya
Vera Stoppioni
Stephen J. Guter
Joseph T. Glessner
Michael Gill
Christopher J. McDougle
Anthony J. Bailey
Margaret A. Pericak-Vance
Joachim Hallmayer
Christine M. Freitag
Penny Farrar
Kirsty Wing
Katherine E. Tansey
Bernadette Rogé
Michael Rutter
Christina Strawbridge
Brett S. Abrahams
Kerstin Wittemeyer
Laura J. Bierut
Tara Paton
Emily L. Crawford
Jonathan L. Haines
Alexander Kolevzon
Gillian Hughes
Lili Senman
James S. Sutcliffe
John B. Gilbert
Katerina Papanikolaou
Andrew R. Carson
Lynne E Cochrane
Regina Regan
Judith Miller
Susanne Thomson
Helen McConachie
Daisuke Sato
Richard Delorme
Jiannis Ragoussis
Eric Fombonne
Clara Lajonchere
Judith Conroy
Dalila Pinto
Aparna Prasad
Naisha Shah
Stanley F. Nelson
Sabine M. Klauck
Catalina Betancur
John B. Vincent
Eftichia Duketis
Jennifer L. Howe
Edwin H. Cook
Xiao-Qing Liu
Catherine Lord
Division of Mental Health and Addiction
Oslo University Hospital [Oslo]
Department of Psychiatry [Pittsburgh]
University of Pittsburgh School of Medicine
Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE)
Program in Genetics and Genomic Biology
Hospital for Sick Children-University of Toronto McLaughlin Centre
Academic Centre on Rare Diseases (ACoRD)
University College Dublin [Dublin] (UCD)
Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA)
BioFIG
Center for Biodiversity, Functional and Integrative Genomics
Department of Neurology
University of California [Los Angeles] (UCLA)
University of California-University of California-David Geffen School of Medicine [Los Angeles]
University of California-University of California
The Wellcome Trust Centre for Human Genetics [Oxford]
University of Oxford [Oxford]
Unidade de Neurodesenvolvimento e Autismo (UNDA)
Hospital Pediatrico de Coimbra
Department of Pharmacy and Biotechnology
Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)
Department of Psychiatry
University of Oxford [Oxford]-Warneford Hospital
Newcomen Centre
Guy's Hospital [London]
Department of Psychiatry and Behavioral Sciences [Stanford]
Stanford Medicine
Stanford University-Stanford University
Child and Adolescent Mental Health
Newcastle University [Newcastle]
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
Goethe-Universität Frankfurt am Main
Department of Child and Adolescent Psychiatry
Institute of psychiatry
Génétique Humaine et Fonctions Cognitives
Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Autism Research Unit
University of Toronto-The Hospital for sick children [Toronto] (SickKids)
Autism and Communicative Disorders Centre
University of Michigan [Ann Arbor]
University of Michigan System-University of Michigan System
Department of Molecular Physiology & Biophysics and Psychiatry
Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience
Department of Statistics
Carnegie Mellon University [Pittsburgh] (CMU)
Scientific Affairs
Autism Speaks
University of North Carolina [Chapel Hill] (UNC)
University of North Carolina System (UNC)-University of North Carolina System (UNC)
University Medical Center [Utrecht]-Brain Center Rudolf Magnus
Service de psychopathologie de l'enfant et de l'adolescent
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
Department of Speech and Hearing Sciences [Washington]
University of Washington [Seattle]
Disciplines of Genetics and Medicine
Memorial University of Newfoundland [St. John's]
John P. Hussman Institute for Human Genomics
University of Miami [Coral Gables]
Department of Child Psychiatry
McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital
McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC)
University of Gothenburg (GU)
The Center for Applied Genomics
Children’s Hospital of Philadelphia (CHOP )
Department of Psychiatry and Behavioural Neurosciences
McMaster University [Hamilton, Ontario]
Manchester Academic Health Sciences Centre
Institute for Juvenile Research-University of Illinois [Chicago] (UIC)
University of Illinois System-University of Illinois System
Department of Pediatrics
Perelman School of Medicine
University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP )
Division of Molecular Genome Analysis
German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)
Human Genetics Center
The University of Texas Health Science Center at Houston (UTHealth)
Department of Medicine
Autism Genetic Resource Exchange
Centre for Integrated Genomic Medical Research, Manchester
University of Manchester [Manchester]
Institut Universitaire d'Hématologie (IUH)
Université Paris Diderot - Paris 7 (UPD7)
Institut Mondor de Recherche Biomédicale (IMRB)
Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Nathan Kline Institute for Psychiatric Research (NKI)
Nathan Kline Institute for Psychiatric Research
New York University [New York] (NYU)
NYU System (NYU)-NYU System (NYU)-NYU Child Study Center
Centre d'Etudes et de Recherches en PsychoPathologie
Université Toulouse - Jean Jaurès (UT2J)
Indiana University School of Medicine
Indiana University System-Indiana University System
Department of Developmental Neuroscience
IRCCS Fondazione Stella Maris [Pisa]
Departments of Psychiatry and Neurology
Department of Psychiatry and Behavioral Sciences
Department of Human Genetics, Los Angeles
David Geffen School of Medicine [Los Angeles]
University of California-University of California-University of California [Los Angeles] (UCLA)
Centre for Addiction and Mental Health
Clarke Institute
University Department of Child Psychiatry
National and Kapodistrian University of Athens (NKUA)
Institutes of Neuroscience and Health and Society
Department of Medicine, Manchester
University of Manchester [Manchester]-School of Epidemiology and Health Science
Carolina Institute for Developmental Disabilities
Social, Genetic and Developmental Psychiatry Centre
Washington University in Saint Louis (WUSTL)
Howard Hughes Medical-Institute Carver College of Medicine-University of Iowa [Iowa City]
Neuropsichiatria Infantile
Ospedale Santa Croce
Child Study Centre
Yale University School of Medicine
Carver College of Medicine [Iowa City]
University of Iowa [Iowa City]-University of Iowa [Iowa City]
University of Alberta
Physiopathologie des Maladies du Système Nerveux Central
Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Vanderbilt Brain Institute
Vanderbilt University School of Medicine [Nashville]
Pathology and Laboratory Medicine
University of Pennsylvania [Philadelphia]
Battelle Center for Mathematical Medicine
Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital
Departments of Biostatistics and Medicine
This research was primarily supported by Autism Speaks (USA), the Health Research Board (HRB
Ireland)
The Medical Research Council (MRC
UK)
Genome Canada/Ontario Genomics Institute
and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH057881, MH061009, MH06359, MH066673, MH077930, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261]
the Canadian Institutes for Health Research (CIHR), Assistance Publique-Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant: Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), GlaxoSmithKline-CIHR Pathfinder Chair (Canada), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health [convention 181 of 19.10.2001], the John P Hussman Foundation (USA), McLaughlin Centre (Canada), Netherlands Organization for Scientific Research [Rubicon 825.06.031], Ontario Ministry of Research and Innovation (Canada), Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801], the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award [075491/Z/04 UK]. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422).
University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles]
University of California (UC)-University of California (UC)
The Hospital for sick children [Toronto] (SickKids)-University of Toronto
Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN)
University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA)
University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine
Yale School of Medicine [New Haven, Connecticut] (YSM)
Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
University of Oxford
University of Oxford-Warneford Hospital
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP )
Université de Toulouse (UT)-Université de Toulouse (UT)
University of Pennsylvania
Betancur, Catalina
Anney R
Klei L
Pinto D
Regan R
Conroy J
Magalhaes TR
Correia C
Abrahams BS
Sykes N
Pagnamenta AT
Almeida J
Bacchelli E
Bailey AJ
Baird G
Battaglia A
Berney T
Bolshakova N
Bölte S
Bolton PF
Bourgeron T
Brennan S
Brian J
Carson AR
Casallo G
Casey J
Chu SH
Cochrane L
Corsello C
Crawford EL
Crossett A
Dawson G
de Jonge M
Delorme R
Drmic I
Duketis E
Duque F
Estes A
Farrar P
Fernandez BA
Folstein SE
Fombonne E
Freitag CM
Gilbert J
Gillberg C
Glessner JT
Goldberg J
Green J
Guter SJ
Hakonarson H
Heron EA
Hill M
Holt R
Howe JL
Hughes G
Hus V
Igliozzi R
Kim C
Klauck SM
Kolevzon A
Korvatska O
Kustanovich V
Lajonchere CM
Lamb JA
Laskawiec M
Leboyer M
Le Couteur A
Leventhal BL
Lionel AC
Liu XQ
Lord C
Lotspeich L
Lund SC
Maestrini E
Mahoney W
Mantoulan C
Marshall CR
McConachie H
McDougle CJ
McGrath J
McMahon WM
Melhem NM
Merikangas A
Migita O
Minshew NJ
Mirza GK
Munson J
Nelson SF
Noakes C
Noor A
Nygren G
Oliveira G
Papanikolaou K
Parr JR
Parrini B
Paton T
Pickles A
Piven J
Posey DJ
Poustka A
Poustka F
Prasad A
Ragoussis J
Renshaw K
Rickaby J
Roberts W
Roeder K
Roge B
Rutter ML
Bierut LJ
Rice JP
Salt J
Sansom K
Sato D
Segurado R
Senman L
Shah N
Sheffield VC
Soorya L
Sousa I
Stoppioni V
Strawbridge C
Tancredi R
Tansey K
Thiruvahindrapduram B
Thompson AP
Thomson S
Tryfon A
Tsiantis J
Van Engeland H
Vincent JB
Volkmar F
Wallace S
Wang K
Wang Z
Wassink TH
Wing K
Wittemeyer K
Wood S
Yaspan BL
Zurawiecki D
Zwaigenbaum L
Betancur C
Buxbaum JD
Cantor RM
Cook EH
Coon H
Cuccaro ML
Gallagher L
Geschwind DH
Gill M
Haines JL
Miller J
Monaco AP
Nurnberger JI Jr
Paterson AD
Pericak-Vance MA
Schellenberg GD
Scherer SW
Sutcliffe JS
Szatmari P
Vicente AM
Vieland VJ
Wijsman EM
Devlin B
Ennis S
Hallmayer J.
Source :
Human Molecular Genetics, Human Molecular Genetics, Oxford University Press (OUP), 2010, 19 (20), pp.4072-82. ⟨10.1093/hmg/ddq307⟩, Anney, R, Klei, L, Pinto, D, Regan, R, Conroy, J, Magalhaes, T R, Correia, C, Abrahams, B S, Sykes, N, Pagnamenta, A T, Almeida, J, Bacchelli, E, Bailey, A J, Baird, G, Battaglia, A, Berney, T, Bolshakova, N, Boelte, S, Bolton, P F, Bourgeron, T, Brennan, S, Brian, J, Carson, A R, Casallo, G, Casey, J, Chu, S H, Cochrane, L, Corsello, C, Crawford, E L, Crossett, A, Dawson, G, de Jonge, M, Delorme, R, Drmic, I, Duketis, E, Duque, F, Estes, A, Farrar, P, Fernandez, B A, Folstein, S E, Fombonne, E, Freitag, C M, Gilbert, J, Gillberg, C, Glessner, J T, Goldberg, J, Green, J, Guter, S J, Hakonarson, H, Heron, E A, Hill, M, Holt, R, Howe, J L, Hughes, G, Hus, V, Igliozzi, R, Kim, C, Klauck, S M, Kolevzon, A, Korvatska, O, Kustanovich, V, Lajonchere, C M, Lamb, J A, Laskawiec, M, Leboyer, M, Le Couteur, A, Leventhal, B L, Lionel, A C, Liu, X-Q, Lord, C, Lotspeich, L, Lund, S C, Maestrini, E, Mahoney, W, Mantoulan, C, Marshall, C R, McConachie, H, McDougle, C J, McGrath, J, McMahon, W M, Melhem, N M, Merikangas, A, Migita, O, Minshew, N J, Mirza, G K, Munson, J, Nelson, S F, Noakes, C, Noor, A, Nygren, G, Oliveira, G, Papanikolaou, K, Parr, J R, Parrini, B, Paton, T, Pickles, A, Piven, J, osey, D J, Poustka, A, Poustka, F, Prasad, A, Ragoussis, J, Renshaw, K, Rickaby, J, Roberts, W, Roeder, K, Roge, B, Rutter, M L, Bierut, L J, Rice, J P, Salt, J, Sansom, K, Sato, D, Segurado, R, Senman, L, Shah, N, Sheffield, V C, Soorya, L, Sousa, I, Stoppioni, V, Strawbridge, C, Tancredi, R, Tansey, K, Thiruvahindrapduram, B, Thompson, A P, Thomson, S, Tryfon, A, Tsiantis, J, Van Engeland, H, Vincent, J B, Volkmar, F, Wallace, S, Wang, K, Wang, Z, Wassink, T H, Wing, K, Wittemeyer, K, Wood, S, Yaspan, B L, Zurawiecki, D, Zwaigenbaum, L, Betancur, C, Buxbaum, J D, Cantor, R M, Cook, E H, Coon, H, Cuccaro, M L, Gallagher, L, Geschwind, D H, Gill, M, Haines, J L, Miller, J, Monaco, A P, Nurnberger, J I, Paterson, A D, Pericak-Vance, M A, Schellenberg, G D, Scherer, S W, Sutcliffe, J S, Szatmari, P, Vicente, A M, Vieland, V J, Wijsman, E M, Devlin, B, Ennis, S & Hallmayer, J 2010, ' A genome-wide scan for common alleles affecting risk for autism ', Human Molecular Genetics, vol. 19, no. 20, ddq307, pp. 4072-4082 . https://doi.org/10.1093/hmg/ddq307, Human Molecular Genetics, 2010, 19 (20), pp.4072-82. ⟨10.1093/hmg/ddq307⟩
Publication Year :
2010
Publisher :
HAL CCSD, 2010.

Abstract

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. Author has checked copyright TS 14.06.13 The subscript characters from the abstract have not copied across properly. TS

Details

Language :
English
ISSN :
09646906 and 14602083
Database :
OpenAIRE
Journal :
Human Molecular Genetics, Human Molecular Genetics, Oxford University Press (OUP), 2010, 19 (20), pp.4072-82. ⟨10.1093/hmg/ddq307⟩, Anney, R, Klei, L, Pinto, D, Regan, R, Conroy, J, Magalhaes, T R, Correia, C, Abrahams, B S, Sykes, N, Pagnamenta, A T, Almeida, J, Bacchelli, E, Bailey, A J, Baird, G, Battaglia, A, Berney, T, Bolshakova, N, Boelte, S, Bolton, P F, Bourgeron, T, Brennan, S, Brian, J, Carson, A R, Casallo, G, Casey, J, Chu, S H, Cochrane, L, Corsello, C, Crawford, E L, Crossett, A, Dawson, G, de Jonge, M, Delorme, R, Drmic, I, Duketis, E, Duque, F, Estes, A, Farrar, P, Fernandez, B A, Folstein, S E, Fombonne, E, Freitag, C M, Gilbert, J, Gillberg, C, Glessner, J T, Goldberg, J, Green, J, Guter, S J, Hakonarson, H, Heron, E A, Hill, M, Holt, R, Howe, J L, Hughes, G, Hus, V, Igliozzi, R, Kim, C, Klauck, S M, Kolevzon, A, Korvatska, O, Kustanovich, V, Lajonchere, C M, Lamb, J A, Laskawiec, M, Leboyer, M, Le Couteur, A, Leventhal, B L, Lionel, A C, Liu, X-Q, Lord, C, Lotspeich, L, Lund, S C, Maestrini, E, Mahoney, W, Mantoulan, C, Marshall, C R, McConachie, H, McDougle, C J, McGrath, J, McMahon, W M, Melhem, N M, Merikangas, A, Migita, O, Minshew, N J, Mirza, G K, Munson, J, Nelson, S F, Noakes, C, Noor, A, Nygren, G, Oliveira, G, Papanikolaou, K, Parr, J R, Parrini, B, Paton, T, Pickles, A, Piven, J, osey, D J, Poustka, A, Poustka, F, Prasad, A, Ragoussis, J, Renshaw, K, Rickaby, J, Roberts, W, Roeder, K, Roge, B, Rutter, M L, Bierut, L J, Rice, J P, Salt, J, Sansom, K, Sato, D, Segurado, R, Senman, L, Shah, N, Sheffield, V C, Soorya, L, Sousa, I, Stoppioni, V, Strawbridge, C, Tancredi, R, Tansey, K, Thiruvahindrapduram, B, Thompson, A P, Thomson, S, Tryfon, A, Tsiantis, J, Van Engeland, H, Vincent, J B, Volkmar, F, Wallace, S, Wang, K, Wang, Z, Wassink, T H, Wing, K, Wittemeyer, K, Wood, S, Yaspan, B L, Zurawiecki, D, Zwaigenbaum, L, Betancur, C, Buxbaum, J D, Cantor, R M, Cook, E H, Coon, H, Cuccaro, M L, Gallagher, L, Geschwind, D H, Gill, M, Haines, J L, Miller, J, Monaco, A P, Nurnberger, J I, Paterson, A D, Pericak-Vance, M A, Schellenberg, G D, Scherer, S W, Sutcliffe, J S, Szatmari, P, Vicente, A M, Vieland, V J, Wijsman, E M, Devlin, B, Ennis, S & Hallmayer, J 2010, ' A genome-wide scan for common alleles affecting risk for autism ', Human Molecular Genetics, vol. 19, no. 20, ddq307, pp. 4072-4082 . https://doi.org/10.1093/hmg/ddq307, Human Molecular Genetics, 2010, 19 (20), pp.4072-82. ⟨10.1093/hmg/ddq307⟩
Accession number :
edsair.doi.dedup.....6db05e54c82d3c414b0cd5e330ddecd2
Full Text :
https://doi.org/10.1093/hmg/ddq307⟩