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Mechelli, R.* ; Umeton, R.* ; Policano, C.* ; Annibali, V.* ; Coarelli, G.* ; Ricigliano, V.A.* ; Vittori, D.* ; Fornasiero, A.* ; Buscarinu, M.C.* ; International Multiple Sclerosis Genetics Consortium (*) ; Wellcome Trust Case Control Consortium 2 (WTCCC2) (Klopp, N. ; Rückert, I.-M. ; Wichmann, H.-E. ; Winkelmann, J.) ; Romano, S.* ; Salvetti, M.* ; Ristori, G.*

A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.

PLoS ONE 8:e63300 (2013)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
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Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 8, Issue: 5, Pages: , Article Number: e63300 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health

30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504200-001
G-503900-002
G-500700-001
G-504000-006
PubMed ID 23696811
DOI 10.1371/journal.pone.0063300
Scopus ID 84877798701
Erfassungsdatum 2013-07-31
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