Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.
AuthorsAnney, Richard J L
Kenny, Elaine M
Yaspan, Brian L
Buxbaum, Joseph D
Buxbaum, Joseph D
AffiliationAutism Genetics Group, Department of Psychiatry, Trinity College Dublin,, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James', Hospital, Dublin, Ireland. email@example.com
Child Development Disorders, Pervasive/diagnosis/*genetics/physiopathology
*Genetic Predisposition to Disease
*Genome-Wide Association Study/methods
Polymorphism, Single Nucleotide
MetadataShow full item record
CitationEur J Hum Genet. 2011 Oct;19(10):1082-9. doi: 10.1038/ejhg.2011.75. Epub 2011 Apr, 27.
JournalEuropean journal of human genetics : EJHG
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.