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 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

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 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

Redescription and phylogenetic relationships of Spermophilus citelloides (Rodentia: Sciuridae: Xerinae), a ground squirrel from the Middle Pleistocene – Holocene of Central Europe

Spermophilus citelloides is a poorly known Old World ground squirrel from the Middle Pleistocene – early Holocene of Central Europe that has only been briefly described previously. Here, we expand our understanding of its craniodental morphology by providing the first detailed description of numerous S. citelloides materials from five Late Pleistocene and early Holocene localities of Hungary and Slovakia. Spermophilus citelloides is recognised as a valid species that is characterised by a shallow, gently domed skull with massive and short rostrum, broad interorbital region, strong zygomatic process of the frontal, posteromedially expanding lacrimal, posteriorly narrowed hard palate, wedge-shaped horizontal process of the palatine, small to absent suboptic foramen, thin condyloid neck of the mandible, M3 possessing a metaloph, and anteroposteriorly elongated m3 with strong hypoconulid and entoconulid. A cladistic analysis of 103 craniodental characters scored across 32 ingroup taxa recovers S. citelloides as the sister taxon of living spotted ground squirrel, S. suslicus, thus confirming the hypothesis of close phylogenetic relationships between the taxa. These relationships are further confirmed by the geometric morphometric analysis of the occlusal outlines of the premolars and molars. The alternative hypothesis allying S. citelloides with S. citellus is not supported by our analyses

Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis

status: publishe