A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous investigations suggested heterogeneity in etiology components and stochasticity in the interaction between genetic and non-genetic factors. To find a unifying model for this evidence, we focused on the recently mapped transient transcriptome (TT), that is mostly coded by intergenic and intronic regions, with half-life of minutes. Through a colocalization analysis, here we demonstrate that genomic regions coding for the TT are significantly enriched for MS-associated GWAS variants and DNA binding sites for molecular transducers mediating putative, non-genetic, determinants of MS (vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction), indicating TT-coding regions as MS etiopathogenetic hotspots. Future research comparing cell-specific transient and stable transcriptomes may clarify the interplay between genetic variability and non-genetic factors causing MS. To this purpose, our colocalization analysis provides a freely available data resource at www.mscoloc.com.

Multiple sclerosis genetic and non-genetic factors interact through the transient transcriptome / Umeton, R.; Bellucci, G.; Bigi, R.; Romano, S.; Buscarinu, M. C.; Renie, R.; Rinaldi, V.; Pizzolato Umeton, R.; Morena, E.; Romano, C.; Mechelli, R.; Salvetti, M.; Ristori, G.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 12:1(2022), p. 7536. [10.1038/s41598-022-11444-w]

Multiple sclerosis genetic and non-genetic factors interact through the transient transcriptome

Umeton R.;Bellucci G.;Bigi R.;Romano S.;Buscarinu M. C.;Renie R.;Rinaldi V.;Morena E.;Romano C.;Mechelli R.;Salvetti M.;Ristori G.
2022

Abstract

A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous investigations suggested heterogeneity in etiology components and stochasticity in the interaction between genetic and non-genetic factors. To find a unifying model for this evidence, we focused on the recently mapped transient transcriptome (TT), that is mostly coded by intergenic and intronic regions, with half-life of minutes. Through a colocalization analysis, here we demonstrate that genomic regions coding for the TT are significantly enriched for MS-associated GWAS variants and DNA binding sites for molecular transducers mediating putative, non-genetic, determinants of MS (vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction), indicating TT-coding regions as MS etiopathogenetic hotspots. Future research comparing cell-specific transient and stable transcriptomes may clarify the interplay between genetic variability and non-genetic factors causing MS. To this purpose, our colocalization analysis provides a freely available data resource at www.mscoloc.com.
2022
Herpesvirus 4, Human; Humans; Transcriptome; Epstein-Barr Virus Infections; Multiple Sclerosis; Vitamin D Deficiency
01 Pubblicazione su rivista::01a Articolo in rivista
Multiple sclerosis genetic and non-genetic factors interact through the transient transcriptome / Umeton, R.; Bellucci, G.; Bigi, R.; Romano, S.; Buscarinu, M. C.; Renie, R.; Rinaldi, V.; Pizzolato Umeton, R.; Morena, E.; Romano, C.; Mechelli, R.; Salvetti, M.; Ristori, G.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 12:1(2022), p. 7536. [10.1038/s41598-022-11444-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1645980
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