Journal Article


James Sutcliffe
Joseph D Buxbaum
Elena Parkhomenka
Louise Gallagher
Brian L Yaspan
Michael Gill
Colm O'Dushlaine
Richard James Leon Anney
Elaine M Kenny



transcription factor polymorphism single nucleotide genome wide association studies health board spectrum analysis psychiatry autism spectrum disorders humans child family cell cycle genetics and genomics physiopathology child development disorders pervasive research design genetics proteins genetic predisposition to disease autistic disorder diagnosis metabolism genome wide association study

Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders. (2011)

Abstract Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings We gratefully acknowledge the families participating in the study and the main funders of the AGP: Autism Speaks (USA), the Health Research Board (HRB, Ireland; AUT/2006/1, AUT/2006/2, PD/2006/48), 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 (NIH Grants: HD055751, HD055782, HD055784, MH52708, MH55284, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institutes for Health Research (CIHR), Assistance Publique ? Ho ? pitaux de Paris (France), Autism Speaks UK, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (Grant: Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundac ?a ? o Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Me ? dicale (France), Fundac ?a ? oparaaCie ? ncia e Tecnologia (Portugal), 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 October 2001), the John P Hussman Foundation (USA), McLaughlin Centre (Canada), Ontario Ministry of Research and Innovation (Canada), 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). DP is supported by fellowships from the Royal Netherlands Academy of Arts and Sciences (TMF/DA/5801) and the Netherlands Organization for Scientific Research (Rubicon 825.06.031). SWS holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto and the Hospital for Sick Children (Canada)
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Full list of authors on original publication

James Sutcliffe, Joseph D Buxbaum, Elena Parkhomenka, Louise Gallagher, Brian L Yaspan, Michael Gill, Colm O'Dushlaine, Richard James Leon Anney, Elaine M Kenny

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Louise Gallagher
Trinity College Dublin
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Michael Gill
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Colm T O'Dushlaine
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Richard Anney
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Elaine Kenny
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