University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Neurology

Publication Date

2021-03-13

Document Type

Article Preprint

Disciplines

Nervous System Diseases | Neuroscience and Neurobiology

Abstract

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).

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.

Keywords

multiple sclerosis, neuroscience, transcriptional regulation, GWAS-associated variants

Rights and Permissions

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.

DOI of Published Version

10.1101/2021.03.12.434773

Source

bioRxiv 2021.03.12.434773; doi: https://doi.org/10.1101/2021.03.12.434773. Link to preprint on bioRxiv.

Comments

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

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.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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