Show simple item record

dc.contributor.authorUmeton, Renato
dc.contributor.authorBellucci, Gianmarco
dc.contributor.authorBigi, Rachele
dc.contributor.authorRomano, Silvia
dc.contributor.authorBuscarinu, Maria Chiara
dc.contributor.authorReniè, Roberta
dc.contributor.authorRinaldi, Virginia
dc.contributor.authorPizzolato Umeton, Raffaella
dc.contributor.authorMorena, Emanuele
dc.contributor.authorRomano, Carmela
dc.contributor.authorMechelli, Rosella
dc.contributor.authorSalvetti, Marco
dc.contributor.authorRistori, Giovanni
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:55:14Z
dc.date.available2022-08-23T15:55:14Z
dc.date.issued2021-03-13
dc.date.submitted2021-03-18
dc.identifier.citation<p>bioRxiv 2021.03.12.434773; doi: https://doi.org/10.1101/2021.03.12.434773. <a href="https://doi.org/10.1101/2021.03.12.434773" target="_blank" title="view preprint on bioRxiv"> Link to preprint on bioRxiv.</a></p>
dc.identifier.doi10.1101/2021.03.12.434773
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29711
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p> <p>The PDF available for download is Version 2 of this preprint. The complete version history of this preprint is available at https://doi.org/10.1101/2021.03.12.434773.</p>
dc.description.abstractA clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous works on these topics suggested a stochastic etiologic model where small-scale random perturbations could eventually reach a threshold for MS onset and progression. A new sequencing technology has mapped the transient transcriptome (TT), including intergenic RNAs, and antisense intronic RNAs. Through a rigorous colocalization analysis, here we show that genomic regions coding for the TT were significantly enriched for both MS-associated GWAS variants, and DNA binding sites for molecular transducers mediating putative, non-genetic, etiopathogenetic factors for MS (e.g., vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction). These results suggest a model whereby TT-coding regions are hotspots of convergence between genetic ad non-genetic factors of risk/protection for MS (and plausibly for other complex disorders). Our colocalization analysis also provides a freely available data resource at www.mscoloc.com for future research on transcriptional regulation in MS.
dc.language.isoen_US
dc.relationNow published in Scientific Reports doi: 10.1038/s41598-022-11444-w
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectmultiple sclerosis
dc.subjectneuroscience
dc.subjecttranscriptional regulation
dc.subjectGWAS-associated variants
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.titleGWAS-associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2953&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1924
dc.identifier.contextkey22098124
refterms.dateFOA2022-08-23T15:55:15Z
html.description.abstract<p><p id="x-x-x-x-p-2">A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous works on these topics suggested a stochastic etiologic model where small-scale random perturbations could eventually reach a threshold for MS onset and progression. A new sequencing technology has mapped the transient transcriptome (TT), including intergenic RNAs, and antisense intronic RNAs. Through a rigorous colocalization analysis, here we show that genomic regions coding for the TT were significantly enriched for both MS-associated GWAS variants, and DNA binding sites for molecular transducers mediating putative, non-genetic, etiopathogenetic factors for MS (e.g., vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction). <p id="x-x-x-x-p-3">These results suggest a model whereby TT-coding regions are hotspots of convergence between genetic ad non-genetic factors of risk/protection for MS (and plausibly for other complex disorders). Our colocalization analysis also provides a freely available data resource at <a href="http://www.mscoloc.com">www.mscoloc.com</a> for future research on transcriptional regulation in MS.</p>
dc.identifier.submissionpathfaculty_pubs/1924
dc.contributor.departmentDepartment of Neurology


Files in this item

Thumbnail
Name:
2021.03.12.434773v2.full.pdf
Size:
1.504Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.