Journal article
Individual common variants exert weak effects on the risk for autism spectrum disorders
Human molecular genetics, Vol.21(21), pp.4781-4792
11/01/2012
DOI: 10.1093/hmg/dds301
PMID: 22843504
Abstract
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.
Details
- Title: Subtitle
- Individual common variants exert weak effects on the risk for autism spectrum disorders
- Creators
- Richard Anney - Division of Mental Health and AddictionLambertus Klei - Department of Psychiatry [Pittsburgh]Dalila Pinto - The Centre for Applied Genomics, TorontoJoana Almeida - Unidade de Neurodesenvolvimento e AutismoElena Bacchelli - Department of Pharmacy and BiotechnologyGillian Baird - Newcomen CentreNadia Bolshakova - Division of Mental Health and AddictionSven Bölte - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyPatrick Bolton - Department of Child and Adolescent PsychiatryThomas Bourgeron - Molecular and Cellular NeurobiologySean Brennan - Division of Mental Health and AddictionJessica Brian - Autism Research UnitJillian Casey - Academic Centre on Rare DiseasesJudith Conroy - Academic Centre on Rare DiseasesCatarina Correia - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Christina Corsello - Autism and Communicative Disorders CentreEmily Crawford - Department of Molecular Physiology & Biophysics and PsychiatryMaretha De Jonge - Department of PsychiatryRichard Delorme - Service de psychopathologie de l'enfant et de l'adolescentFrederico Duque - Unidade de Neurodesenvolvimento e AutismoEftichia Duketis - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyAnnette Estes - Department of Speech and Hearing Sciences [Washington]Penny Farrar - The Wellcome Trust Centre for Human Genetics [Oxford]Bridget Fernandez - Disciplines of Genetics and MedicineSusan Folstein - Department of PsychiatryEric Fombonne - Research Unit on Children's Psychosocial MaladjustmentJohn Gilbert - John P. Hussman Institute for Human GenomicsChristopher Gillberg - Department of Child and Adolescent PsychiatryJoseph Glessner - The Center for Applied GenomicsAndrew Green - University College DublinJonathan Green - Manchester Academic Health Sciences CentreStephen Guter - Department of Disability and Human DevelopmentElizabeth Heron - Division of Mental Health and AddictionRichard Holt - The Wellcome Trust Centre for Human Genetics [Oxford]Jennifer Howe - The Centre for Applied Genomics, TorontoGillian Hughes - Division of Mental Health and AddictionVanessa Hus - Autism and Communicative Disorders CentreRoberta Igliozzi - Department of Psychiatry and Behavioral Sciences [Stanford]Suma Jacob - Department of Disability and Human DevelopmentGraham Kenny - Division of Mental Health and AddictionCecilia Kim - The Center for Applied GenomicsAlexander Kolevzon - Human Genetics CenterVlad Kustanovich - Autism Genetic Resource ExchangeClara Lajonchere - Autism Genetic Resource ExchangeJanine Lamb - Centre for Integrated Genomic Medical Research, ManchesterMiriam Law-Smith - Division of Mental Health and AddictionMarion Leboyer - Institut Mondor de Recherche BiomédicaleAnn Le Couteur - Department of Child and Adolescent PsychiatryBennett Leventhal - Department of Child and Adolescent PsychiatryXiao-Qing Liu - Program in Genetics and Genomic BiologyFrances Lombard - Division of Mental Health and AddictionCatherine Lord - Autism and Communicative Disorders CentreLinda Lotspeich - Department of Psychiatry and Behavioral Sciences [Stanford]Sabata Lund - Department of Molecular Physiology & Biophysics and PsychiatryTiago Magalhaes - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Carine Mantoulan - Centre de Référence du Syndrome de Prader-WilliChristopher Mcdougle - Department of PsychiatryNadine Melhem - Department of Psychiatry [Pittsburgh]Alison Merikangas - Division of Mental Health and AddictionNancy Minshew - Department of Psychiatry [Pittsburgh]Ghazala Mirza - The Wellcome Trust Centre for Human Genetics [Oxford]Jeff Munson - Department of Psychiatry and Behavioral SciencesCarolyn Noakes - Autism Research UnitGudrun Nygren - Department of Child and Adolescent PsychiatryKaterina Papanikolaou - University Department of Child PsychiatryAlistair 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 BiologyAndrew Pickles - Department of Medicine, ManchesterDavid Posey - Department of PsychiatryFritz Poustka - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyJiannis Ragoussis - The Wellcome Trust Centre for Human Genetics [Oxford]Regina Regan - Academic Centre on Rare DiseasesWendy Roberts - Autism Research UnitKathryn Roeder - Department of StatisticsBernadette Roge - Octogone Unité de Recherche InterdisciplinaireMichael Rutter - Social, Genetic and Developmental Psychiatry CentreSabine Schlitt - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyNaisha Shah - Academic Centre on Rare DiseasesVal Sheffield - Department of PediatricsLatha Soorya - Human Genetics CenterInês Sousa - The Wellcome Trust Centre for Human Genetics [Oxford]Vera Stoppioni - Neuropsichiatria InfantileNuala 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 NeurosciencesSusanne Thomson - Department of Molecular Physiology & Biophysics and PsychiatryAna Tryfon - Human Genetics CenterJohn Tsiantis - University Department of Child PsychiatryHerman Van Engeland - Department of PsychiatryJohn Vincent - Department of PsychiatryFred Volkmar - Child Study CentreJacob Vorstman - Department of PsychiatrySimon Wallace - Department of PsychiatryKirsty Wing - The Wellcome Trust Centre for Human Genetics [Oxford]Kerstin Wittemeyer - Department of PsychiatryShawn Wood - Department of Psychiatry [Pittsburgh]Danielle Zurawiecki - Human Genetics CenterLonnie Zwaigenbaum - Department of PediatricsAnthony Bailey - Department of Psychiatry
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.21(21), pp.4781-4792
- DOI
- 10.1093/hmg/dds301
- PMID
- 22843504
- NLM abbreviation
- Hum Mol Genet
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Publisher
- Oxford University Press (OUP)
- Language
- English
- Date published
- 11/01/2012
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065392202771
Metrics
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