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

Hdl Handle:
http://hdl.handle.net/10147/207779
Title:
Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.
Authors:
Anney, Richard J L; Kenny, Elaine M; O'Dushlaine, Colm; Yaspan, Brian L; Parkhomenka, Elena; Buxbaum, Joseph D; Sutcliffe, James; Gill, Michael; Gallagher, Louise; Buxbaum, Joseph D; Sutcliffe, James; Gill, Michael; Gallagher, Louise
Affiliation:
Autism Genetics Group, Department of Psychiatry, Trinity College Dublin,, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James', Hospital, Dublin, Ireland. anneyr@tcd.ie
Citation:
Eur J Hum Genet. 2011 Oct;19(10):1082-9. doi: 10.1038/ejhg.2011.75. Epub 2011 Apr, 27.
Journal:
European journal of human genetics : EJHG
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207779
DOI:
10.1038/ejhg.2011.75
PubMed ID:
21522181
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.
Language:
eng
MeSH:
Autistic Disorder/diagnosis/*genetics/physiopathology; Child; Child Development Disorders, Pervasive/diagnosis/*genetics/physiopathology; Family; *Genetic Predisposition to Disease; *Genome-Wide Association Study/methods; Humans; Polymorphism, Single Nucleotide; Proteins/*genetics/metabolism; Research Design
ISSN:
1476-5438 (Electronic); 1018-4813 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorAnney, Richard J Len_GB
dc.contributor.authorKenny, Elaine Men_GB
dc.contributor.authorO'Dushlaine, Colmen_GB
dc.contributor.authorYaspan, Brian Len_GB
dc.contributor.authorParkhomenka, Elenaen_GB
dc.contributor.authorBuxbaum, Joseph Den_GB
dc.contributor.authorSutcliffe, Jamesen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorGallagher, Louiseen_GB
dc.contributor.authorBuxbaum, Joseph Den_GB
dc.contributor.authorSutcliffe, Jamesen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorGallagher, Louiseen_GB
dc.date.accessioned2012-02-01T10:44:26Z-
dc.date.available2012-02-01T10:44:26Z-
dc.date.issued2012-02-01T10:44:26Z-
dc.identifier.citationEur J Hum Genet. 2011 Oct;19(10):1082-9. doi: 10.1038/ejhg.2011.75. Epub 2011 Apr, 27.en_GB
dc.identifier.issn1476-5438 (Electronic)en_GB
dc.identifier.issn1018-4813 (Linking)en_GB
dc.identifier.pmid21522181en_GB
dc.identifier.doi10.1038/ejhg.2011.75en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207779-
dc.description.abstractRecent 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAutistic Disorder/diagnosis/*genetics/physiopathologyen_GB
dc.subject.meshChilden_GB
dc.subject.meshChild Development Disorders, Pervasive/diagnosis/*genetics/physiopathologyen_GB
dc.subject.meshFamilyen_GB
dc.subject.mesh*Genetic Predisposition to Diseaseen_GB
dc.subject.mesh*Genome-Wide Association Study/methodsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshProteins/*genetics/metabolismen_GB
dc.subject.meshResearch Designen_GB
dc.titleGene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.en_GB
dc.contributor.departmentAutism Genetics Group, Department of Psychiatry, Trinity College Dublin,, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James', Hospital, Dublin, Ireland. anneyr@tcd.ieen_GB
dc.identifier.journalEuropean journal of human genetics : EJHGen_GB
dc.description.provinceLeinster-

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