GWAS-associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis [preprint]
Buscarinu, Maria Chiara
Umeton, Raffaella Pizzolato
UMass Chan AffiliationsDepartment of Neurology
Nervous System Diseases
Neuroscience and Neurobiology
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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.
bioRxiv 2021.03.12.434773; doi: https://doi.org/10.1101/2021.03.12.434773. Link to preprint on bioRxiv.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29711
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
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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.