Identification of a two-loci epistatic interaction associated with susceptibility to rheumatoid arthritis through reverse engineering and multifactor dimensionality reduction

Antonio Julià, Jason Moore, Laia Miquel, Cayetano Alegre, Pere Barceló, Marylyn Ritchie, Sara Marsal

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Altered synovial fibroblast (SF) transcriptional activity is a key factor in the disease progression of rheumatoid arthritis (RA). To determine the transcriptional regulatory network associated with SF response to an RA proinflammatory stimulus we applied a CARRIE reverse engineering approach to microarray gene expression data from SFs treated with RA synovial fluid. The association of the inferred gene network with RA susceptibility was further analyzed by a case-control study of promoter single-nucleotide polymorphisms, and the presence of epistatic interactions was determined using the multifactor dimensionality reduction methodology. Our findings suggest that a specific NF-κB transcriptional regulatory network of 13 genes is associated with SF response to RA proinflammatory stimulus and identify a significant epistatic association of two of its genes, IL6 and IL4I1, with RA susceptibility.

Original languageEnglish (US)
Pages (from-to)6-13
Number of pages8
JournalGenomics
Volume90
Issue number1
DOIs
StatePublished - Jul 1 2007

All Science Journal Classification (ASJC) codes

  • Genetics

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