dc.contributor.author	Rogozin, Igor B.
dc.contributor.author	Gertz, E. Michael
dc.contributor.author	Baranov, Pavel V.
dc.contributor.author	Poliakov, Eugenia
dc.contributor.author	Schaffer, Alejandro A.
dc.contributor.funder	National Eye Institute
dc.contributor.funder	U.S. National Library of Medicine
dc.contributor.funder	National Institutes of Health
dc.date.accessioned	2018-09-27T12:08:16Z
dc.date.available	2018-09-27T12:08:16Z
dc.date.issued	2018
dc.description.abstract	We previously proposed that changes in the efficiency of protein translation are associated with autism spectrum disorders (ASDs). This hypothesis connects environmental factors and genetic factors because each can alter translation efficiency. For genetic factors, we previously tested our hypothesis using a small set of ASD-associated genes, a small set of ASD-associated variants, and a statistic to quantify by how much a single nucleotide variant (SNV) in a protein coding region changes translation speed. In this study, we confirm and extend our hypothesis using a published set of 1,800 autism quartets (parents, one affected child and one unaffected child) and genome-wide variants. Then, we extend the test statistic to combine translation efficiency with other possibly relevant variables: ribosome profiling data, presence/absence of CpG dinucleotides, and phylogenetic conservation. The inclusion of ribosome profiling abundances strengthens our results for male–male sibling pairs. The inclusion of CpG information strengthens our results for female–female pairs, giving an insight into the significant gender differences in autism incidence. By combining the single-variant test statistic for all variants in a gene, we obtain a single gene score to evaluate how well a gene distinguishes between affected and unaffected siblings. Using statistical methods, we compute gene sets that have some power to distinguish between affected and unaffected siblings by translation efficiency of gene variants. Pathway and enrichment analysis of those gene sets suggest the importance of Wnt signaling pathways, some other pathways related to cancer, ATP binding, and ATP-ase pathways in the etiology of ASDs.	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Rogozin, I. B., Gertz, E. M., Baranov, P. V., Poliakov, E. and Schaffer, A. A. (2018) 'Genome-wide changes in protein translation efficiency are associated with autism', Genome Biology and Evolution, 10(8), pp. 1902-1919. doi:10.1093/gbe/evy146	en
dc.identifier.doi	10.1093/gbe/evy146
dc.identifier.endpage	1919
dc.identifier.issn	1759-6653
dc.identifier.issued	8
dc.identifier.journaltitle	Genome Biology and Evolution	en
dc.identifier.startpage	1902
dc.identifier.uri	https://hdl.handle.net/10468/6931
dc.identifier.volume	10
dc.language.iso	en	en
dc.publisher	Oxford University Press	en
dc.relation.uri	https://academic.oup.com/gbe/article/10/8/1902/5050464
dc.rights	© 2018, the Authors. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject	Autism spectrum disorder	en
dc.subject	Ribosome profiling	en
dc.subject	Codon usage	en
dc.subject	Expression	en
dc.subject	CpG dinucleotides	en
dc.subject	Single nucleotide variant	en
dc.title	Genome-wide changes in protein translation efficiency are associated with autism	en
dc.type	Article (peer-reviewed)	en

Genome-wide changes in protein translation efficiency are associated with autism

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