SEARCHSYSTEMATIC_REVIEWneurology, psychiatry

systematic_review·neurology, psychiatry, pediatrics, systematic review, biomedical research·PMC10270643

A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

PLOS ONE · 7 authors, 7 centres

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This PROSPERO-registered systematic review searched multiple databases from January 2000 to May 2022 for studies examining differential expression of non-coding RNA genes in human ASD cohorts versus non-ASD controls. Forty-eight eligible studies were included, with the majority focusing on microRNA (miRNA). The review identified four miRNA genes with consistent differential expression in the same direction in at least three separate studies: increased expression of miR-106b-5p, miR-155-5p, and miR-146a-5p, and decreased expression of miR-328-3p. However, overall results were often inconsistent across studies.

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systematic_review

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neurology

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ORIGINAL PAPER

PMC10270643

A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

PLOS ONE

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ABSTRACT

Abstract Aims To identify differential expression of shorter non-coding RNA (ncRNA) genes associated with autism spectrum disorders (ASD). Background ncRNA are functional molecules that derive from non-translated DNA sequence. The HUGO Gene Nomenclature Committee (HGNC) have approved ncRNA gene classes with alignment to the reference human genome. One subset is microRNA (miRNA), which are highly conserved, short RNA molecules that regulate gene expression by direct post-transcriptional repression of messenger RNA. Several miRNA genes are implicated in the development and regulation of the nervous system. Expression of miRNA genes in ASD cohorts have been examined by multiple research groups. Other shorter classes of ncRNA have been examined less. A comprehensive systematic review examining expression of shorter ncRNA gene classes in ASD is timely to inform the direction of research. Methods We extracted data from studies examining ncRNA gene expression in ASD compared with non-ASD controls. We included studies on miRNA, piwi-interacting RNA (piRNA), small NF90 (ILF3) associated RNA (snaR), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), transfer RNA (tRNA), vault RNA (vtRNA) and Y RNA. The following electronic databases were searched: Cochrane Library, EMBASE, PubMed, Web of Science, PsycINFO, ERIC, AMED and CINAHL for papers published from January 2000 to May 2022. Studies were screened by two independent investigators with a third resolving discrepancies. Data was extracted from eligible papers. Results Forty-eight eligible studies were included in our systematic review with the majority examining miRNA gene expression alone. Sixty-four miRNA genes had differential expression in ASD compared to controls as reported in two or more studies, but often in opposing directions. Four miRNA genes had differential expression in the same direction in the same tissue type in at least 3 separate studies. Increased expression was reported in miR-106b-5p , miR-155-5p and miR-146a-5p in blood, post-mortem brain, and across several tissue types, respectively. Decreased expression was reported in miR-328-3p in bloods samples. Seven studies examined differential expression from other classes of ncRNA, including piRNA, snRNA, snoRNA and Y RNA. No individual ncRNA genes were reported in more than one study. Six studies reported differentially expressed snoRNA genes in ASD. A meta-analysis was not possible because of inconsistent methodologies, disparate tissue types examined, and varying forms of data presented. Conclusion There is limited but promising evidence associating the expression of certain miRNA genes and ASD, although the studies are of variable methodological quality and the results are largely inconsistent. There is emerging evidence associating differential expression of snoRNA genes in ASD. It is not currently possible to say whether the reports of differential expression in ncRNA may relate to ASD aetiology, a response to shared environmental factors linked to ASD such as sleep and nutrition, other molecular functions, human diversity, or chance findings. To improve our understanding of any potential association, we recommend improved and standardised methodologies and reporting of raw data. Further high-quality research is required to shine a light on possible associations, which may yet yield important information.

CITATION EXPORT

Jon Stott, Thomas Wright, Jannah Holmes et al.. A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders. PLOS ONE. (2023). https://doi.org/10.1371/journal.pone.0287131

AUTHORS

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Jon Stott, Thomas Wright, Jannah Holmes, Julie Wilson, Sam Griffiths-Jones, Deborah Foster, Barry Wright

1Child Oriented Mental Health Intervention Collaborative (COMIC), University of York in Collaboration with Leeds and York Partnership NHS Foundation Trust, York, United Kingdom
2Tees, Esk & Wear Valleys NHS Foundation Trust, Foss Park Hospital, York, United Kingdom
3Manchester Centre for Genomic Medicine, Clinical Genetics Service, Saint Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
4Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
5Hull York Medical School, University of York, Heslington, York, United Kingdom
6Department of Mathematics, University of York, Heslington, York, United Kingdom
7Universita Politecnica delle Marche, ITALY