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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
- 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.
- Subjects :
- Genetics
0303 health sciences
Multiple sclerosis
Cytomegalovirus
Biology
medicine.disease_cause
medicine.disease
Interactome
Epstein–Barr virus
Transcriptome
03 medical and health sciences
0302 clinical medicine
Genotype
Genetic predisposition
medicine
Gene
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....adc50ba5a9b18c3f577343c94e6603ef
- Full Text :
- https://doi.org/10.1101/624049