Eur J Hum Genet. 2011 Oct;19(10):1082-9. doi: 10.1038/ejhg.2011.75. Epub 2011 Apr 27.
Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.
Anney RJ,
Kenny EM,
O'Dushlaine C,
Yaspan BL,
Parkhomenka E,
Buxbaum JD,
Sutcliffe J,
Gill M,
Gallagher L;
Autism Genome Project,
Buxbaum JD,
Sutcliffe J,
Gill M,
Gallagher L.
Bailey AJ, Fernandez BA, Szatmari P, Scherer SW, Patterson A, Marshall CR, Pinto D, Vincent JB, Fombonne E, Betancur C, Delorme R, Leboyer M, Bourgeron T, Mantoulan C, Roge B, Tauber M, Freitag CM, Poustka F, Duketis E, Klauck SM, Poustka A, Papanikolaou K, Tsiantis J, Gallagher L, Gill M, Anney R, Bolshakova N, Brennan S, Hughes G, McGrath J, Merikangas A, Ennis S, Green A, Casey JP, Conroy JM, Regan R, Shah N, Maestrini E, Bacchelli E, Minopoli F, Stoppioni V, Battaglia A, Igliozzi R, Parrini B, Tancredi R, Oliveira G, Almeida J, Duque F, Vicente A, Correia C, Magalhaes TR, Gillberg C, Nygren G, de Jonge M, Van Engeland H, Vorstman JA, Wittemeyer K, Baird G, Bolton PF, Rutter ML, Green J, Lamb JA, Pickles A, Parr JR, Couteur AL, Berney T, McConachie H, Wallace S, Coutanche M, Foley S, White K, Monaco AP, Holt R, Farrar P, Pagnamenta AT, Mirza GK, Ragoussis J, Sousa I, Sykes N, Wing K, Hallmayer J, Cantor RM, Nelson SF, Geschwind DH, Abrahams BS, Volkmar F, Pericak-Vance MA, Cuccaro ML, Gilbert J, Cook EH, Guter SJ, Jacob S, Nurnberger JI, McDougle CJ, Posey DJ, Lord C, Corsello C, Hus V, Buxbaum JD, Kolevzon A, Soorya L, Parkhomenko E, Leventhal BL, Dawson G, Vieland VJ, Hakonarson H, Glessner JT, Kim C, Wang K, Schellenberg GD, Devlin B, Klei L, Minshew N, Sutcliffe JS, Haines JL, Lund SC, Thomson S, Yaspan BL, Coon H, Miller J, McMahon WM, Munson J, Estes A, Wijsman EM.
Source
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
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.
- PMID:
- 21522181
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3190264
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