Department of Neurology
Nervous System Diseases | Neuroscience and Neurobiology
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.
multiple sclerosis, neuroscience, transcriptional regulation, GWAS-associated variants
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DOI of Published Version
bioRxiv 2021.03.12.434773; doi: https://doi.org/10.1101/2021.03.12.434773. Link to preprint on bioRxiv.
Umeton R, Bellucci G, Bigi R, Romano S, Buscarinu MC, Reniè R, Rinaldi V, Umeton RP, Morena E, Romano C, Mechelli R, Salvetti M, Ristori G. (2021). GWAS-associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.03.12.434773. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1924
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