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Significant enrichment of Herpesvirus interactors in GWAS data suggests causal inferences for the association between Epstein Barr virus and multiple sclerosis

Authors :
Rosella Mechelli
Imsgc
Arianna Fornasiero
Cinthia Farina
Diego Centonze
Renato Umeton
Giovanni Ristori
Michela Ferraldeschi
Marco Salvetti
Wtccc
Sundararajan Srinivasan
Publication Year :
2019
Publisher :
Cold Spring Harbor Laboratory, 2019.

Abstract

SUMMARYWe exploited genetic information to assess the role of non-genetic factors in multifactorial diseases. To this aim we isolated candidate “interactomes” (i.e. groups of genes whose products are known to physically interact with environmental exposures and biological processes, plausibly relevant for disease pathogenesis) and analyzed nominal statistical evidence of association with genetic predisposition to multiple sclerosis (MS) and other inflammatory and non-inflammatory complex disorders. The interaction between genotype and Herpesviruses emerged as specific for MS, with Epstein Barr virus (EBV) showing higher levels of significance compared to Human Herpesvirus 8 (HHV8) and, more evidently, to cytomegalovirus (CMV). In accord with this result, when we classified the MS-associated genes contained in the interactomes into canonical pathways, the analysis converged towards biological functions of B cells, in particular the CD40 pathway. When we analyzed peripheral blood transcriptomes in persons with MS, we found a significant dysregulation of MS-associated genes belonging to the EBV interactome in primary progressive MS. This study indicates that the interaction between herpesviruses and predisposing genetic background is of causal significance in MS, and provides a mechanistic explanation for the long-recognized association between EBV and this condition.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....adc50ba5a9b18c3f577343c94e6603ef
Full Text :
https://doi.org/10.1101/624049