A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.

Jillian P Casey; Tiago Magalhaes; Judith Conroy; Regina Regan; Naisha Shah; Ann Anney; Denis C Shields; Brett S Abrahams; Joana Almeida; Elena Bacchelli; Anthony J Bailey; Gillian Gill; Agatino Battaglia; Tom Berney; Nadia Bolshakova; Patrick F Bolton; Thomas Bourgeron; Sean Brennan; Phil Cali; Catarina Correia; Christina Corsello; Marc Coutanche; Geraldine Dawson; Maretha de Jonge; Richard Delorme; Eftichia Duketis; Fred Duque; Ann Estes; Penny Farrar; Bridget A Fernandez; Susan E Folstein; Suzanne Foley; Eric Fombonne; Christine M Freitag; John Gilbert; Christopher Gill; Joseph Glessner; Jonathan Green; Stephen J Guter; Hakon Hakonarson; Richard Holt; Vanessa Hus; Roberta Igliozzi; Cecilia Kim; Sabine M Klauck; Alexander Kolevzon; Janine A Lamb; Marion Leboyer; Ann Le Couteur; Bennett L Leventhal; Catherine Lord; Sabata C Lund; Elena Maestrini; Carine Mantoulan; Christian R Marshall; Helen Mcconachie; Christopher J Mcdougle; Jane Mcgrath; William M Mcmahon; Alison Merikangas; Judith Miller; Fiorella Minopoli; Ghazala K Mirza; Jeff Munson; Stanley F Nelson; Gudrun Nygren; Guiomar Oliveira; Alistair T Pagnamenta; Katerina Papanikolaou; Jeremy R Parr; Barbara Parrini; Andrew Pickles; Dalila Pinto; Joseph Piven; David J Posey; Annemarie Poustka; Fritz Poustka; Jiannis Ragoussis; Bernadette Roge; Michael Rutter; Ana F Sequeira; Latha Soorya; Inês Sousa; Nuala Sykes; Vera Stoppioni; Raffaella Tancredi; Maïté Tauber; Ann P Thompson; Susanne Thomson; John Tsiantis; Herman van Engeland; John B Vincent; Fred Volkmar; Jacob a S Vorstman; Simon Wallace; Kai Wang; Thomas H Wassink; Kathy White; Kirsty Wing; Kerstin Wittemeyer; Brian L Yaspan; Lonnie Zwaigenbaum; Catalina Betancur; Joseph D Buxbaum; Rita M Cantor; Edwin H Cook; Hilary Coon; Michael Cuccaro; Daniel H. Geschwind; Jonathan L Haines; Joachim Hallmayer; Anthony P Monaco; John I Nurnberger; Margaret A Pericak-Vance; Gerard D Schellenberg; Stephen W Scherer; James S Sutcliffe; Peter Szatmari; Veronica J Vieland; Ellen M Wijsman; Andrew Green; Michael Gill; Louise Gallagher; Astrid Vicente; Sean Ennis

doi:10.1007/s00439-011-1094-6

Journal Articles Human Genetics Year : 2012

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.

, , , , , , , , , (1) , , (2) , (3) , , , , (4, 5) , , , , , , , , (6) , (7) , , , , (8) , , , (9) , (7) , , , , (10) , , , (11) , , , , (12) , , , (13) , , , , , (1) , , (14, 15) , , , , , , (16) , , , , , , (17) , , , , , , (14) , , , , (7) , , , , , , , , , , (18) , (19) , , , , (20) , , , , , , (21) , , , , (22) , (23) , (24) , , , , , , (25) , , , , , , (26) , , (27) , , , , , , ,

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27

Jillian P Casey

Function : Author

Tiago Magalhaes

Function : Author

Judith Conroy

Function : Author

Regina Regan

Function : Author

Naisha Shah

Function : Author

Ann Anney

Function : Author

Denis C Shields

Function : Author

Brett S Abrahams

Function : Author

Joana Almeida

Function : Author

Elena Bacchelli

Function : Author

Alma Mater Studiorum Università di Bologna = University of Bologna

Anthony J Bailey

Function : Author

Gillian Gill

Function : Author

Open University of Israël

Agatino Battaglia

Function : Author

IRCCS Fondazione Stella Maris [Pisa]

Tom Berney

Function : Author

Nadia Bolshakova

Function : Author

Patrick F Bolton

Function : Author

Thomas Bourgeron

Function : Author
PersonId : 747963
IdHAL : thomas-bourgeron
ORCID : 0000-0001-8164-9220
IdRef : 119761955

Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions

Institut Pasteur [Paris]

Sean Brennan

Function : Author

Phil Cali

Function : Author

Catarina Correia

Function : Author

Christina Corsello

Function : Author

Marc Coutanche

Function : Author

Geraldine Dawson

Function : Author

Maretha de Jonge

Function : Author

Richard Delorme

Function : Author

AP-HP Hôpital universitaire Robert-Debré [Paris]

Eftichia Duketis

Function : Author

Goethe University Frankfurt

Fred Duque

Function : Author

Ann Estes

Function : Author

Penny Farrar

Function : Author

Bridget A Fernandez

Function : Author

Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada]

Susan E Folstein

Function : Author

Suzanne Foley

Function : Author

Eric Fombonne

Function : Author

McGill University = Université McGill [Montréal, Canada]

Christine M Freitag

Function : Author

Goethe University Frankfurt

John Gilbert

Function : Author

Christopher Gill

Function : Author

Joseph Glessner

Function : Author

Jonathan Green

Function : Author
PersonId : 763155
ORCID : 0000-0002-5003-0203

Johns Hopkins University

Stephen J Guter

Function : Author

Hakon Hakonarson

Function : Author
PersonId : 763145
ORCID : 0000-0003-2814-7461

Richard Holt

Function : Author

Autism Research Centre and Section of Developmental Psychiatry

Vanessa Hus

Function : Author

Roberta Igliozzi

Function : Author

Cecilia Kim

Function : Author

Sabine M Klauck

Function : Author

German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]

Alexander Kolevzon

Function : Author

Janine A Lamb

Function : Author

Marion Leboyer

Function : Author
PersonId : 756830
ORCID : 0000-0001-5473-3697
IdRef : 089352475

Psychiatrie génétique

Ann Le Couteur

Function : Author

Bennett L Leventhal

Function : Author

Catherine Lord

Function : Author

Sabata C Lund

Function : Author

Elena Maestrini

Function : Author

Alma Mater Studiorum Università di Bologna = University of Bologna

Carine Mantoulan

Function : Author

Christian R Marshall

Function : Author

The Hospital for sick children [Toronto]

University of Toronto

Helen Mcconachie

Function : Author

Christopher J Mcdougle

Function : Author

Jane Mcgrath

Function : Author

William M Mcmahon

Function : Author

Alison Merikangas

Function : Author

Judith Miller

Function : Author

Australian Resources Research Centre, Kensington,

Fiorella Minopoli

Function : Author

Ghazala K Mirza

Function : Author

Jeff Munson

Function : Author

Stanley F Nelson

Function : Author

Gudrun Nygren

Function : Author

Guiomar Oliveira

Function : Author

Sécurité et Qualité des Produits d'Origine Végétale

Alistair T Pagnamenta

Function : Author

Katerina Papanikolaou

Function : Author

Jeremy R Parr

Function : Author

Barbara Parrini

Function : Author

Andrew Pickles

Function : Author

Dalila Pinto

Function : Author

The Hospital for sick children [Toronto]

Joseph Piven

Function : Author

David J Posey

Function : Author

Annemarie Poustka

Function : Author

Fritz Poustka

Function : Author

Goethe University Frankfurt

Jiannis Ragoussis

Function : Author
PersonId : 763156
ORCID : 0000-0002-8515-0934

Bernadette Roge

Function : Author

Michael Rutter

Function : Author

Ana F Sequeira

Function : Author

Latha Soorya

Function : Author

Inês Sousa

Function : Author

Nuala Sykes

Function : Author

Vera Stoppioni

Function : Author

Raffaella Tancredi

Function : Author

Maïté Tauber

Function : Author
PersonId : 1097566
ORCID : 0000-0002-0363-7862
IdRef : 085677167

Centre Hospitalier Universitaire de Toulouse

Ann P Thompson

Function : Author

School of Chemistry

Susanne Thomson

Function : Author

John Tsiantis

Function : Author

Herman van Engeland

Function : Author

John B Vincent

Function : Author

DLR Institut für Planetenforschung

Fred Volkmar

Function : Author

Jacob a S Vorstman

Function : Author

Simon Wallace

Function : Author

Kai Wang

Function : Author
PersonId : 763158
ORCID : 0000-0001-6269-3517

Thomas H Wassink

Function : Author

Kathy White

Function : Author

Department of Human Genetics

Kirsty Wing

Function : Author

Kerstin Wittemeyer

Function : Author

Brian L Yaspan

Function : Author

Lonnie Zwaigenbaum

Function : Author

University of Alberta

Catalina Betancur

Function : Author
PersonId : 13320
IdHAL : catalina-betancur
ORCID : 0000-0002-3327-4804
IdRef : 180835750

Génétique de l'autisme = Genetics of Autism

Joseph D Buxbaum

Function : Author

Seaver Autism Center for Research and Treatment

Rita M Cantor

Function : Author

Edwin H Cook

Function : Author

Hilary Coon

Function : Author

Michael Cuccaro

Function : Author

Daniel H. Geschwind

Function : Author

Jonathan L Haines

Function : Author

Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier

Joachim Hallmayer

Function : Author

Anthony P Monaco

Function : Author

John I Nurnberger

Function : Author

Margaret A Pericak-Vance

Function : Author

Gerard D Schellenberg

Function : Author

Stephen W Scherer

Function : Author

University of Koblenz-Landau

James S Sutcliffe

Function : Author

Peter Szatmari

Function : Author

McMaster University [Hamilton, Ontario]

Veronica J Vieland

Function : Author

Ellen M Wijsman

Function : Author

Andrew Green

Function : Author

Michael Gill

Function : Author

Louise Gallagher

Function : Author

Astrid Vicente

Function : Author

Sean Ennis

Function : Author

Abstract

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.

Domains

Neurons and Cognition [q-bio.NC]

Fichier principal

s00439-011-1094-6 (1).pdf (589.47 Ko)

Origin	Publication funded by an institution

Gestionnaire HAL-UPMC : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-01548905

Submitted on : Wednesday, June 28, 2017-11:09:38 AM

Last modification on : Tuesday, September 17, 2024-10:16:17 AM

Long-term archiving on : Monday, January 22, 2018-10:14:46 PM

Dates and versions

hal-01548905 , version 1 (28-06-2017)

Licence

Attribution

Identifiers

HAL Id : hal-01548905 , version 1
DOI : 10.1007/s00439-011-1094-6
PUBMED : 21996756
PUBMEDCENTRAL : PMC3303079

Cite

Jillian P Casey, Tiago Magalhaes, Judith Conroy, Regina Regan, Naisha Shah, et al.. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.. Human Genetics, 2012, 131 (4), pp.565-79. ⟨10.1007/s00439-011-1094-6⟩. ⟨hal-01548905⟩

Export

BibTeX XML-TEI Dublin Core DC Terms EndNote DataCite

Collections

PASTEUR UNIV-PARIS7 UNIV-AVIGNON UPMC CNRS ICG NPS INC-CNRS IBPS NPS-01 CHIMIE UNIV-MONTPELLIER SORBONNE-UNIVERSITE SU-SCIENCES INRAE UP-SCIENCES SQPOV FRM HUM-GEN-COGN-FUN PASTEUR_UMR3571 INRAEPACA

994 View

235 Download

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.

Abstract

Domains

Dates and versions

Licence

Identifiers

Cite

Export

Collections

Altmetric

Share