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

Rosella Mechelli; Renato Umeton; Claudia Policano; Viviana Annibali; Giulia Coarelli; Vito A G Ricigliano; Danila Vittori; Arianna Fornasiero; Maria Chiara Buscarinu; Silvia Romano; Marco Salvetti; Giovanni Ristori; International Multiple Sclerosis Genetics Consortium; Per Soelberg Sørensen

doi:10.1371/journal.pone.0063300

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

Rosella Mechelli, Renato Umeton, Claudia Policano, Viviana Annibali, Giulia Coarelli, Vito A G Ricigliano, Danila Vittori, Arianna Fornasiero, Maria Chiara Buscarinu, Silvia Romano, Marco Salvetti, Giovanni Ristori, International Multiple Sclerosis Genetics Consortium, Per Soelberg Sørensen

Department of Clinical Medicine

26 Citations (Scopus)

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.

Original language	English
Article number	e63300
Journal	P L o S One
Volume	8
Issue number	5
Number of pages	9
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0063300
Publication status	Published - 16 May 2013

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Mechelli, R., Umeton, R., Policano, C., Annibali, V., Coarelli, G., Ricigliano, V. A. G., Vittori, D., Fornasiero, A., Buscarinu, M. C., Romano, S., Salvetti, M., Ristori, G., Consortium, I. M. S. G., & Sørensen, P. S. (2013). A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis. P L o S One, 8(5), [e63300]. https://doi.org/10.1371/journal.pone.0063300

Mechelli, R, Umeton, R, Policano, C, Annibali, V, Coarelli, G, Ricigliano, VAG, Vittori, D, Fornasiero, A, Buscarinu, MC, Romano, S, Salvetti, M, Ristori, G, Consortium, IMSG & Sørensen, PS 2013, 'A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis', P L o S One, vol. 8, no. 5, e63300. https://doi.org/10.1371/journal.pone.0063300

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

Abstract

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