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

Richard J.L. Anney; Elaine M. Kenny; Colm O'Dushlaine; Brian L. Yaspan; Elena Parkhomenka; Joseph D. Buxbaum; James Sutcliffe; Michael Gill; Louise Gallagher; Anthony J. Bailey; Bridget A. Fernandez; Peter Szatmari; Stephen W. Scherer; Andrew Patterson; Christian R. Marshall; Dalila Pinto; John B. Vincent; Eric Fombonne; Catalina Betancur; Richard Delorme; Marion Leboyer; Thomas Bourgeron; Carine Mantoulan; Bernadette Roge; Mäité Tauber; Christine M. Freitag; Fritz Poustka; Eftichia Duketis; Sabine M. Klauck; Annemarie Poustka; Katerina Papanikolaou; John Tsiantis; Nadia Bolshakova; Sean Brennan; Gillian Hughes; Jane McGrath; Alison Merikangas; Sean Ennis; Andrew Green; Jillian P. Casey; Judith M. Conroy; Regina Regan; Naisha Shah; Elena Maestrini; Elena Bacchelli; Fiorella Minopoli; Vera Stoppioni; Agatino Battaglia; Roberta Igliozzi; Suma Jacob; Autism Genome Project

doi:10.1038/ejhg.2011.75

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

Richard J.L. Anney, Elaine M. Kenny, Colm O'Dushlaine, Brian L. Yaspan, Elena Parkhomenka, Joseph D. Buxbaum, James Sutcliffe, Michael Gill, Louise Gallagher, Anthony J. Bailey, Bridget A. Fernandez, Peter Szatmari, Stephen W. Scherer, Andrew Patterson, Christian R. Marshall, Dalila Pinto, John B. Vincent, Eric Fombonne, Catalina Betancur, Richard DelormeMarion Leboyer, Thomas Bourgeron, Carine Mantoulan, Bernadette Roge, Mäité Tauber, Christine M. Freitag, Fritz Poustka, Eftichia Duketis, Sabine M. Klauck, Annemarie Poustka, Katerina Papanikolaou, John Tsiantis, Nadia Bolshakova, Sean Brennan, Gillian Hughes, Jane McGrath, Alison Merikangas, Sean Ennis, Andrew Green, Jillian P. Casey, Judith M. Conroy, Regina Regan, Naisha Shah, Elena Maestrini, Elena Bacchelli, Fiorella Minopoli, Vera Stoppioni, Agatino Battaglia, Roberta Igliozzi, Suma Jacob, Autism Genome Project

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1082-1089
Number of pages	8
Journal	European Journal of Human Genetics
Volume	19
Issue number	10
DOIs	https://doi.org/10.1038/ejhg.2011.75
State	Published - Oct 2011

Bibliographical note

Publisher Copyright:
© 2011 Macmillan Publishers Limited All rights reserved.

Keywords

autism
family-based association test
gene ontology
genome-wide association analysis
pathway analysis

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10.1038/ejhg.2011.75

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Anney, R. J. L., Kenny, E. M., O'Dushlaine, C., Yaspan, B. L., Parkhomenka, E., Buxbaum, J. D., Sutcliffe, J., Gill, M., Gallagher, L., Bailey, A. J., Fernandez, B. A., Szatmari, P., Scherer, S. W., Patterson, A., Marshall, C. R., Pinto, D., Vincent, J. B., Fombonne, E., Betancur, C., ... Autism Genome Project (2011). Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders. European Journal of Human Genetics, 19(10), 1082-1089. https://doi.org/10.1038/ejhg.2011.75

Anney, RJL, Kenny, EM, O'Dushlaine, C, Yaspan, BL, Parkhomenka, E, 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, 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, Jacob, S & Autism Genome Project 2011, 'Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders', European Journal of Human Genetics, vol. 19, no. 10, pp. 1082-1089. https://doi.org/10.1038/ejhg.2011.75

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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.",

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AU - Poustka, Annemarie

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

Abstract

Bibliographical note

Keywords

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