title: A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.
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.
authors.affiliation: Centre for Experimental Neurological Therapies, S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Rome, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Mechelli
authors.forename: Renato
authors.initials: R
authors.lastname: Umeton
authors.forename: Claudia
authors.initials: C
authors.lastname: Policano
authors.forename: Viviana
authors.initials: V
authors.lastname: Annibali
authors.forename: Giulia
authors.initials: G
authors.lastname: Coarelli
authors.forename: Vito A G
authors.initials: VA
authors.lastname: Ricigliano
authors.forename: Danila
authors.initials: D
authors.lastname: Vittori
authors.forename: Arianna
authors.initials: A
authors.lastname: Fornasiero
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Buscarinu
authors.forename: Silvia
authors.initials: S
authors.lastname: Romano
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ristori
mesh_terms: D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding