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-1β (IL-1β) 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-1β C-511T and the interferon-γ 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.
Interleukin-1 gene complex single nucleotide polymorphisms in systemic sclerosis : a further step ahead / L. Beretta, F. Cappiello, J.H. Moore, R. Scorza. - In: HUMAN IMMUNOLOGY. - ISSN 0198-8859. - 69:3(2008 Mar), pp. 187-192.
|Titolo:||Interleukin-1 gene complex single nucleotide polymorphisms in systemic sclerosis : a further step ahead|
BERETTA, LUCA (Primo)
CAPPIELLO, FRANCESCA (Secondo)
SCORZA, RAFFAELLA (Ultimo)
|Parole Chiave:||Epistasis; Lung fibrosis; Single nucleotide polymorphism; Systemic sclerosis|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||mar-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.humimm.2007.12.006|
|Appare nelle tipologie:||01 - Articolo su periodico|