title: Interleukin-1 gene complex single nucleotide polymorphisms in systemic sclerosis: a further step ahead.
abstract: Gene-gene and gene-environment interactions are difficult to detect by traditional parametric computational approaches. Novel nonparametric and model-free strategies, such as the multifactor dimensionality reduction (MDR) algorithm, are thus emerging as practical and feasible methods of analysis to model high-order epistatic interactions, integrating and complementing traditional logistic approaches. With traditional methods of analysis we showed that the interleukin-1 beta (IL-1 beta) C+3962T single nucleotide polymorphism (SNP), along with the Sc70 antibody and the diffuse cutaneous subset of systemic sclerosis, are important risk factors for the development of a severe ventilatory restriction in patients with systemic sclerosis (SSc); however the interactions among these and other genetic and environmental attributes were difficult to model. On the contrary, the MDR analysis detected significant two- or three-way interactions in the presence of nonlinearity. The best model identified by the multifactor dimensionality reduction algorithm included the antibody subset, the IL-1 beta C-511T and the interferon-gamma AUTR5644T SNPs, with a testing accuracy of 85% (p < 0.001) and a cross-validation consistency of 10/10. This model outperformed any one- to-three-way model constructed by considering the three factors with main independent effects identified by traditional computational approaches. Epistatic interactions among IL-1 gene complex SNPs and clinical or environmental factors are more important than the singe attributes in the development of severe ventilatory restriction in SSc patients.
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena and University of Milan, Milan, Italy. lorberimm@hotmail.com <lorberimm@hotmail.com>
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Francesca
authors.initials: F
authors.lastname: Cappiello
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
mesh_terms: D000328:Adult; D000465:Algorithms; D000974:Antibodies, Antinuclear / Q000276:immunology; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D004843:Epistasis, Genetic; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D012123:Pulmonary Ventilation / Q000276:immunology; D012307:Risk Factors; D045743:Scleroderma, Diffuse / Q000235:genetics / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000503:physiopathology; D018709:Statistics, Nonparametric
chemical_list: D000974:Antibodies, Antinuclear; D053583:Interleukin-1beta; D007371:Interferon-gamma; D004264:DNA Topoisomerases, Type I