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

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Item Type:Article
Title:A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis
Creators Name:Mechelli, R. and Umeton, R. and Policano, C. and Annibali, V. and Coarelli, G. and Ricigliano, V.A.G. and Vittori, D. and Fornasiero, A. and Buscarinu, M.C. and Romano, S. and Salvetti, M. and Ristori, G.
Abstract: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.
Keywords:Genome-Wide Association Study, Genotype, Multiple Sclerosis, Protein Binding
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:8
Number:5
Page Range:e63300
Date:16 May 2013
Additional Information:Frauke Zipp and Carmen Infante-Duarte are members of the International Multiple Sclerosis Genetics Consortium (IMSGC) and Wellcome Trust Case Control Consortium,2 (WTCCC2)
Official Publication:https://doi.org/10.1371/journal.pone.0063300
PubMed:View item in PubMed

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