title: Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis candidate genes.
abstract: Rheumatoid arthritis (RA, MIM 180300) is a chronic and complex autoimmune disease. Using the North American Rheumatoid Arthritis Consortium (NARAC) data set provided in Genetic Analysis Workshop 16 (GAW16), we used the genotype-trait distortion (GTD) scores and proposed analysis procedures to capture the gene-gene interaction effects of multiple susceptibility gene regions on RA. In this paper, we focused on 27 RA candidate gene regions (531 SNPs) based on a literature search. Statistical significance was evaluated using 1000 permutations. HLADRB1 was found to have strong marginal association with RA. We identified 14 significant interactions (p < 0.01), which were aggregated into an association network among 12 selected candidate genes PADI4, FCGR3, TNFRSF1B, ITGAV, BTLA, SLC22A4, IL3, VEGF, TNF, NFKBIL1, TRAF1-C5, and MIF. Based on our and other contributors' findings during the GAW16 conference, we further studied 24 candidate regions with 336 SNPs. We found 23 significant interactions (p-value < 0.01), nine interactions in addition to our initial findings, and the association network was extended to include candidate genes HLA-A, HLA-B, HLA-C, CTLA4, and IL6. As we will discuss in this paper, the reported possible interactions between genes may suggest potential biological activities of RA.
authors.affiliation: Department of Statistics, Columbia University, 1255 Amsterdam Avenue, 10th Floor, MC44690, New York, New York 10027, USA. ch2526@columbia.edu.
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Cong
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Qiao
authors.forename: Shaw-Hwa
authors.initials: SH
authors.lastname: Lo
authors.forename: Tian
authors.initials: T
authors.lastname: Zheng