Individual common variants exert weak effects on the risk for autism spectrum disorders

Richard Anney; Lambertus Klei; Dalila Pinto; Joana Almeida; Elena Bacchelli; Gillian Baird; Nadia Bolshakova; Sven Bölte; Patrick Bolton; Thomas Bourgeron; Sean Brennan; Jessica Brian; Jillian Casey; Judith Conroy; Catarina Correia; Christina Corsello; Emily Crawford; Maretha De Jonge; Richard Delorme; Eftichia Duketis; Frederico Duque; Annette Estes; Penny Farrar; Bridget Fernandez; Susan Folstein; Eric Fombonne; John Gilbert; Christopher Gillberg; Joseph Glessner; Andrew Green; Jonathan Green; Stephen Guter; Elizabeth Heron; Richard Holt; Jennifer Howe; Gillian Hughes; Vanessa Hus; Roberta Igliozzi; Suma Jacob; Graham Kenny; Cecilia Kim; Alexander Kolevzon; Vlad Kustanovich; Clara Lajonchere; Janine Lamb; Miriam Law-Smith; Marion Leboyer; Ann Le Couteur; Bennett Leventhal; Xiao-Qing Liu; Frances Lombard; Catherine Lord; Linda Lotspeich; Sabata Lund; Tiago Magalhaes; Carine Mantoulan; Christopher Mcdougle; Nadine Melhem; Alison Merikangas; Nancy Minshew; Ghazala Mirza; Jeff Munson; Carolyn Noakes; Gudrun Nygren; Katerina Papanikolaou; Alistair Pagnamenta; Barbara Parrini; Tara Paton; Andrew Pickles; David Posey; Fritz Poustka; Jiannis Ragoussis; Regina Regan; Wendy Roberts; Kathryn Roeder; Bernadette Roge; Michael Rutter; Sabine Schlitt; Naisha Shah; Val Sheffield; Latha Soorya; Inês Sousa; Vera Stoppioni; Nuala Sykes; Raffaella Tancredi; Ann Thompson; Susanne Thomson; Ana Tryfon; John Tsiantis; Herman Van Engeland; John Vincent; Fred Volkmar; Jacob Vorstman; Simon Wallace; Kirsty Wing; Kerstin Wittemeyer; Shawn Wood; Danielle Zurawiecki; Lonnie Zwaigenbaum; Anthony Bailey; Gillberg Neuropsychiatry Centre

doi:10.1093/hmg/dds301

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Individual common variants exert weak effects on the risk for autism spectrum disorders

Journal article

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Peer reviewed

Individual common variants exert weak effects on the risk for autism spectrum disorders

Richard Anney, Lambertus Klei, Dalila Pinto, Joana Almeida, Elena Bacchelli, Gillian Baird, Nadia Bolshakova, Sven Bölte, Patrick Bolton, Thomas Bourgeron, …

Human molecular genetics, Vol.21(21), pp.4781-4792

11/01/2012

DOI: https://doi.org/10.1093/hmg/dds301

PMID: 22843504

Abstract

Genetics

Life Sciences

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

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Title: Individual common variants exert weak effects on the risk for autism spectrum disorders
Creators: Richard Anney - Division of Mental Health and Addiction
Lambertus Klei - Department of Psychiatry [Pittsburgh]
Dalila Pinto - The Centre for Applied Genomics, Toronto
Joana Almeida - Unidade de Neurodesenvolvimento e Autismo
Elena Bacchelli - Department of Pharmacy and Biotechnology
Gillian Baird - Newcomen Centre
Nadia Bolshakova - Division of Mental Health and Addiction
Sven Bölte - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
Patrick Bolton - Department of Child and Adolescent Psychiatry
Thomas Bourgeron - Molecular and Cellular Neurobiology
Sean Brennan - Division of Mental Health and Addiction
Jessica Brian - Autism Research Unit
Jillian Casey - Academic Centre on Rare Diseases
Judith Conroy - Academic Centre on Rare Diseases
Catarina Correia - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
Christina Corsello - Autism and Communicative Disorders Centre
Emily Crawford - Department of Molecular Physiology & Biophysics and Psychiatry
Maretha De Jonge - Department of Psychiatry
Richard Delorme - Service de psychopathologie de l'enfant et de l'adolescent
Eftichia Duketis - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
Frederico Duque - Unidade de Neurodesenvolvimento e Autismo
Annette Estes - Department of Speech and Hearing Sciences [Washington]
Penny Farrar - The Wellcome Trust Centre for Human Genetics [Oxford]
Bridget Fernandez - Disciplines of Genetics and Medicine
Susan Folstein - Department of Psychiatry
Eric Fombonne - Research Unit on Children's Psychosocial Maladjustment
John Gilbert - John P. Hussman Institute for Human Genomics
Christopher Gillberg - Department of Child and Adolescent Psychiatry
Joseph Glessner - The Center for Applied Genomics
Andrew Green - Academic Centre on Rare Diseases
Jonathan Green - Manchester Academic Health Sciences Centre
Stephen Guter - Department of Disability and Human Development
Elizabeth Heron - Division of Mental Health and Addiction
Richard Holt - The Wellcome Trust Centre for Human Genetics [Oxford]
Jennifer Howe - The Centre for Applied Genomics, Toronto
Gillian Hughes - Division of Mental Health and Addiction
Vanessa Hus - Autism and Communicative Disorders Centre
Roberta Igliozzi - Department of Psychiatry and Behavioral Sciences [Stanford]
Suma Jacob - Department of Disability and Human Development
Graham Kenny - Division of Mental Health and Addiction
Cecilia Kim - The Center for Applied Genomics
Alexander Kolevzon - Human Genetics Center
Vlad Kustanovich - Autism Genetic Resource Exchange
Clara Lajonchere - Autism Genetic Resource Exchange
Janine Lamb - Centre for Integrated Genomic Medical Research, Manchester
Miriam Law-Smith - Division of Mental Health and Addiction
Marion Leboyer - Institut Mondor de Recherche Biomédicale
Ann Le Couteur - Department of Child and Adolescent Psychiatry
Bennett Leventhal - Department of Child and Adolescent Psychiatry
Xiao-Qing Liu - Program in Genetics and Genomic Biology
Frances Lombard - Division of Mental Health and Addiction
Catherine Lord - Autism and Communicative Disorders Centre
Linda Lotspeich - Department of Psychiatry and Behavioral Sciences [Stanford]
Sabata Lund - Department of Molecular Physiology & Biophysics and Psychiatry
Tiago Magalhaes - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
Carine Mantoulan - Centre de Référence du Syndrome de Prader-Willi
Christopher Mcdougle - Department of Psychiatry
Nadine Melhem - Department of Psychiatry [Pittsburgh]
Alison Merikangas - Division of Mental Health and Addiction
Nancy Minshew - Department of Psychiatry [Pittsburgh]
Ghazala Mirza - The Wellcome Trust Centre for Human Genetics [Oxford]
Jeff Munson - Department of Psychiatry and Behavioral Sciences
Carolyn Noakes - Autism Research Unit
Gudrun Nygren - Department of Child and Adolescent Psychiatry
Katerina Papanikolaou - University Department of Child Psychiatry
Alistair Pagnamenta - The Wellcome Trust Centre for Human Genetics [Oxford]
Barbara Parrini - Department of Psychiatry and Behavioral Sciences [Stanford]
Tara Paton - Program in Genetics and Genomic Biology
Andrew Pickles - Department of Medicine, Manchester
David Posey - Department of Psychiatry
Fritz Poustka - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
Jiannis Ragoussis - The Wellcome Trust Centre for Human Genetics [Oxford]
Regina Regan - Academic Centre on Rare Diseases
Wendy Roberts - Autism Research Unit
Kathryn Roeder - Department of Statistics
Bernadette Roge - Octogone Unité de Recherche Interdisciplinaire
Michael Rutter - Social, Genetic and Developmental Psychiatry Centre
Sabine Schlitt - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
Naisha Shah - Academic Centre on Rare Diseases
Val Sheffield - Department of Pediatrics
Latha Soorya - Human Genetics Center
Inês Sousa - The Wellcome Trust Centre for Human Genetics [Oxford]
Vera Stoppioni - Neuropsichiatria Infantile
Nuala Sykes - The Wellcome Trust Centre for Human Genetics [Oxford]
Raffaella Tancredi - Department of Psychiatry and Behavioral Sciences [Stanford]
Ann Thompson - Department of Psychiatry and Behavioural Neurosciences
Susanne Thomson - Department of Molecular Physiology & Biophysics and Psychiatry
Ana Tryfon - Human Genetics Center
John Tsiantis - University Department of Child Psychiatry
Herman Van Engeland - Department of Psychiatry
John Vincent - Department of Psychiatry
Fred Volkmar - Child Study Centre
Jacob Vorstman - Department of Psychiatry
Simon Wallace - Department of Psychiatry
Kirsty Wing - The Wellcome Trust Centre for Human Genetics [Oxford]
Kerstin Wittemeyer - Department of Psychiatry
Shawn Wood - Department of Psychiatry [Pittsburgh]
Danielle Zurawiecki - Human Genetics Center
Lonnie Zwaigenbaum - Department of Pediatrics
Anthony Bailey - Department of Psychiatry
Gillberg Neuropsychiatry Centre
Publication Details: Human molecular genetics, Vol.21(21), pp.4781-4792
Date published: 11/01/2012
Publisher: Oxford University Press (OUP)
Academic Unit: Applied Psychology (GSAPP)
Language: English
Resource Type: Journal article
Identifiers: 991031665441304646