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

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 grou...

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Main Authors: Rosella Mechelli, Renato Umeton, Claudia Policano, Viviana Annibali, Giulia Coarelli, Vito A G Ricigliano, Danila Vittori, Arianna Fornasiero, Maria Chiara Buscarinu, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium,2, Silvia Romano, Marco Salvetti, Giovanni Ristori
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063300&type=printable
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author Rosella Mechelli
Renato Umeton
Claudia Policano
Viviana Annibali
Giulia Coarelli
Vito A G Ricigliano
Danila Vittori
Arianna Fornasiero
Maria Chiara Buscarinu
International Multiple Sclerosis Genetics Consortium
Wellcome Trust Case Control Consortium,2
Silvia Romano
Marco Salvetti
Giovanni Ristori
author_facet Rosella Mechelli
Renato Umeton
Claudia Policano
Viviana Annibali
Giulia Coarelli
Vito A G Ricigliano
Danila Vittori
Arianna Fornasiero
Maria Chiara Buscarinu
International Multiple Sclerosis Genetics Consortium
Wellcome Trust Case Control Consortium,2
Silvia Romano
Marco Salvetti
Giovanni Ristori
author_sort Rosella Mechelli
collection DOAJ
description 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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spelling doaj-art-b4d7db5e189c4ff185f998145fd067392025-08-20T03:26:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6330010.1371/journal.pone.0063300A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.Rosella MechelliRenato UmetonClaudia PolicanoViviana AnnibaliGiulia CoarelliVito A G RiciglianoDanila VittoriArianna FornasieroMaria Chiara BuscarinuInternational Multiple Sclerosis Genetics ConsortiumWellcome Trust Case Control Consortium,2Silvia RomanoMarco SalvettiGiovanni RistoriThough 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063300&type=printable
spellingShingle Rosella Mechelli
Renato Umeton
Claudia Policano
Viviana Annibali
Giulia Coarelli
Vito A G Ricigliano
Danila Vittori
Arianna Fornasiero
Maria Chiara Buscarinu
International Multiple Sclerosis Genetics Consortium
Wellcome Trust Case Control Consortium,2
Silvia Romano
Marco Salvetti
Giovanni Ristori
A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
PLoS ONE
title A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
title_full A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
title_fullStr A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
title_full_unstemmed A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
title_short A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
title_sort candidate interactome aggregate analysis of genome wide association data in multiple sclerosis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063300&type=printable
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