Author:
Umeton Renato,Bellucci Gianmarco,Bigi Rachele,Romano Silvia,Buscarinu Maria Chiara,Reniè Roberta,Rinaldi Virginia,Umeton Raffaella Pizzolato,Morena Emanuele,Romano Carmela,Mechelli Rosella,Salvetti Marco,Ristori Giovanni
Abstract
AbstractA clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. We previously suggested a stochastic etiologic model where small-scale random perturbations could reach a threshold for MS development. The recently described mapping of the transient transcriptome (TT), including intergenic and intronic RNAs, seems appropriate to verify this model through a rigorous colocalization analysis. We show that genomic regions coding for the TT were significantly enriched for 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 (www.mscoloc.com) for future research on MS transcriptional regulation.
Publisher
Cold Spring Harbor Laboratory