title: Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.
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.
authors.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
authors.forename: Richard J L
authors.initials: RJ
authors.lastname: Anney
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Kenny
authors.forename: Colm
authors.initials: C
authors.lastname: O'Dushlaine
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.forename: Elena
authors.initials: E
authors.lastname: Parkhomenka
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: James
authors.initials: J
authors.lastname: Sutcliffe
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Louise
authors.initials: L
authors.lastname: Gallagher
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: James
authors.initials: J
authors.lastname: Sutcliffe
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Louise
authors.initials: L
authors.lastname: Gallagher
mesh_terms: D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005190:Family; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012107:Research Design
chemical_list: D011506:Proteins