RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation.

Citation metadata

From: Molecular Autism(Vol. 10, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Article
Length: 9,571 words
Lexile Measure: 1630L

Document controls

Main content

Abstract :

Background A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC. Methods Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N = 36) and (b) within discordant ASC MZ twin pairs (total N = 11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis. Results In the discordant twin analysis, three genes showed evidence for DE at FDR Limitations Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis. Conclusions Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals. Keywords: Autism spectrum disorder, Immune, MZ twins, RNA-seq, Gene expression, DNA methylation, Transcriptomics, Epigenomics, Discordance

Source Citation

Source Citation   

Gale Document Number: GALE|A607355849