Genome-Wide Changes in Protein Translation Efficiency Are Associated with Autism. (7th July 2018)

• Record Type: Journal Article
• Authors: Rogozin, Igor B; Gertz, E Michael; Baranov, Pasha V; Poliakov, Eugenia; Schaffer, Alejandro A
• Editors: Martin, Bill
• Is Part Of: Genome biology and evolution. Volume 10:Number 8(2018:Aug.)
• Page Start: 1902
• Page End: 1919
• Publication Date: 2018-07-07
• Subjects: autism spectrum disorder -- ribosome profiling -- codon usage -- expression -- CpG dinucleotides -- single nucleotide variant; Genomics -- Periodicals; Genes -- Periodicals; 572.8605
• DOI: 10.1093/gbe/evy146
• Languages: English
• ISSNs: 1759-6653

Abstract

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.