Journal article
A genome-wide scan for common alleles affecting risk for autism
Human molecular genetics, Vol.19(20), pp.4072-4082
10/15/2010
DOI: 10.1093/hmg/ddq307
PMCID: PMC2947401
PMID: 20663923
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.
Details
- Title: Subtitle
- A genome-wide scan for common alleles affecting risk for autism
- Creators
- Richard Anney - Division of Mental Health and AddictionLambertus Klei - Department of Psychiatry [Pittsburgh]Dalila Pinto - Program in Genetics and Genomic BiologyRegina Regan - Academic Centre on Rare DiseasesJudith Conroy - Academic Centre on Rare DiseasesTiago Magalhaes - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Catarina Correia - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Brett Abrahams - Department of NeurologyNuala Sykes - The Wellcome Trust Centre for Human Genetics [Oxford]Alistair Pagnamenta - The Wellcome Trust Centre for Human Genetics [Oxford]Joana Almeida - Unidade de Neurodesenvolvimento e AutismoElena Bacchelli - Department of Pharmacy and BiotechnologyAnthony Bailey - Department of PsychiatryGillian Baird - Newcomen CentreAgatino Battaglia - Department of Psychiatry and Behavioral Sciences [Stanford]Tom Berney - Child and Adolescent Mental HealthNadia 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 - Génétique Humaine et Fonctions CognitivesSean Brennan - Division of Mental Health and AddictionJessica Brian - Autism Research UnitAndrew Carson - Program in Genetics and Genomic BiologyGuillermo Casallo - Program in Genetics and Genomic BiologyJillian Casey - Academic Centre on Rare DiseasesSu Chu - Department of Psychiatry [Pittsburgh]Lynne Cochrane - Division of Mental Health and AddictionChristina Corsello - Autism and Communicative Disorders CentreEmily Crawford - Department of Molecular Physiology & Biophysics and PsychiatryAndrew Crossett - Department of StatisticsGeraldine Dawson - Scientific AffairsMaretha De Jonge - Department of PsychiatryRichard Delorme - Service de psychopathologie de l'enfant et de l'adolescentIrene Drmic - Autism Research UnitEftichia Duketis - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyFrederico Duque - Unidade de Neurodesenvolvimento e AutismoAnnette 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 - John P. Hussman Institute for Human GenomicsEric Fombonne - Department of Child PsychiatryChristine Freitag - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyJohn Gilbert - John P. Hussman Institute for Human GenomicsChristopher Gillberg - Department of Child and Adolescent PsychiatryJoseph Glessner - The Center for Applied GenomicsJeremy Goldberg - Department of Psychiatry and Behavioural NeurosciencesJonathan Green - Manchester Academic Health Sciences CentreStephen Guter - Department of PsychiatryHakon Hakonarson - The Center for Applied GenomicsElizabeth Heron - Division of Mental Health and AddictionMatthew Hill - Division of Mental Health and AddictionRichard Holt - The Wellcome Trust Centre for Human Genetics [Oxford]Jennifer Howe - Program in Genetics and Genomic BiologyGillian Hughes - Division of Mental Health and AddictionVanessa Hus - Autism and Communicative Disorders CentreRoberta Igliozzi - Department of Psychiatry and Behavioral Sciences [Stanford]Cecilia Kim - The Center for Applied GenomicsSabine Klauck - Division of Molecular Genome AnalysisAlexander Kolevzon - Human Genetics CenterOlena Korvatska - Department of MedicineVlad Kustanovich - Autism Genetic Resource ExchangeClara Lajonchere - Autism Genetic Resource ExchangeJanine Lamb - Centre for Integrated Genomic Medical Research, ManchesterMagdalena Laskawiec - Department of Psychiatry [Pittsburgh]Marion Leboyer - Institut Universitaire d'HématologieAnn Le Couteur - Child and Adolescent Mental HealthBennett Leventhal - Nathan Kline Institute for Psychiatric ResearchAnath Lionel - Program in Genetics and Genomic BiologyXiao-Qing Liu - Program in Genetics and Genomic BiologyCatherine Lord - Autism and Communicative Disorders CentreLinda Lotspeich - Department of Psychiatry and Behavioral Sciences [Stanford]Sabata Lund - Department of Molecular Physiology & Biophysics and PsychiatryElena Maestrini - Department of Pharmacy and BiotechnologyWilliam Mahoney - Department of PediatricsCarine Mantoulan - Centre d'Etudes et de Recherches en PsychoPathologieChristian Marshall - Program in Genetics and Genomic BiologyHelen Mcconachie - Child and Adolescent Mental HealthChristopher Mcdougle - Department of PsychiatryJane Mcgrath - Division of Mental Health and AddictionWilliam Mcmahon - Department of Developmental NeuroscienceNadine Melhem - Department of Psychiatry [Pittsburgh]Alison Merikangas - Division of Mental Health and AddictionOhsuke Migita - Program in Genetics and Genomic BiologyNancy Minshew - Departments of Psychiatry and NeurologyGhazala Mirza - The Wellcome Trust Centre for Human Genetics [Oxford]Jeff Munson - Department of Psychiatry and Behavioral SciencesStanley Nelson - Department of Human Genetics, Los AngelesCarolyn Noakes - Autism Research UnitAbdul Noor - Centre for Addiction and Mental HealthGudrun Nygren - Department of Child and Adolescent PsychiatryGuiomar Oliveira - Unidade de Neurodesenvolvimento e AutismoKaterina Papanikolaou - University Department of Child PsychiatryJeremy Parr - Institutes of Neuroscience and Health and SocietyBarbara Parrini - Department of Psychiatry and Behavioral Sciences [Stanford]Tara Paton - Program in Genetics and Genomic BiologyAndrew Pickles - Department of Medicine, ManchesterJoseph Piven - Carolina Institute for Developmental DisabilitiesDavid Posey - Department of PsychiatryAnnemarie Poustka - Division of Molecular Genome AnalysisFritz Poustka - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
- Contributors
- Val C Sheffield (Contributor) - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.19(20), pp.4072-4082
- Publisher
- Oxford University Press (OUP)
- DOI
- 10.1093/hmg/ddq307
- PMID
- 20663923
- PMCID
- PMC2947401
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English
- Date published
- 10/15/2010
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070334102771
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