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Rare structural variation of synapse and neurotransmission genes in autism
Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commona...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314176/ https://www.ncbi.nlm.nih.gov/pubmed/21358714 http://dx.doi.org/10.1038/mp.2011.10 |
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author | Gai, X Xie, H M Perin, J C Takahashi, N Murphy, K Wenocur, A S D'arcy, M O'Hara, R J Goldmuntz, E Grice, D E Shaikh, T H Hakonarson, H Buxbaum, J D Elia, J White, P S |
author_facet | Gai, X Xie, H M Perin, J C Takahashi, N Murphy, K Wenocur, A S D'arcy, M O'Hara, R J Goldmuntz, E Grice, D E Shaikh, T H Hakonarson, H Buxbaum, J D Elia, J White, P S |
author_sort | Gai, X |
collection | PubMed |
description | Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci. |
format | Online Article Text |
id | pubmed-3314176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-33141762012-03-30 Rare structural variation of synapse and neurotransmission genes in autism Gai, X Xie, H M Perin, J C Takahashi, N Murphy, K Wenocur, A S D'arcy, M O'Hara, R J Goldmuntz, E Grice, D E Shaikh, T H Hakonarson, H Buxbaum, J D Elia, J White, P S Mol Psychiatry Original Article Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci. Nature Publishing Group 2012-04 2011-03-01 /pmc/articles/PMC3314176/ /pubmed/21358714 http://dx.doi.org/10.1038/mp.2011.10 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Gai, X Xie, H M Perin, J C Takahashi, N Murphy, K Wenocur, A S D'arcy, M O'Hara, R J Goldmuntz, E Grice, D E Shaikh, T H Hakonarson, H Buxbaum, J D Elia, J White, P S Rare structural variation of synapse and neurotransmission genes in autism |
title | Rare structural variation of synapse and neurotransmission genes in autism |
title_full | Rare structural variation of synapse and neurotransmission genes in autism |
title_fullStr | Rare structural variation of synapse and neurotransmission genes in autism |
title_full_unstemmed | Rare structural variation of synapse and neurotransmission genes in autism |
title_short | Rare structural variation of synapse and neurotransmission genes in autism |
title_sort | rare structural variation of synapse and neurotransmission genes in autism |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314176/ https://www.ncbi.nlm.nih.gov/pubmed/21358714 http://dx.doi.org/10.1038/mp.2011.10 |
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