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.

Comments

This is the publisher pdf of Chien-Hsun Huang, Lei Cong, Jun Xie, Bo Qiao, Shaw-Hwa Lo, Tian Zheng. Rheumatoid Arthritis-Associated Gene-Gene Interaction Network for Rheumatoid Arthritis Candidate Genes. BMC Proceedings 2009, 3(Suppl 7):S75 (15 December 2009) and is available at: 10.1186/1753-6561-3-S7-S75.

Date of this Version

12-15-2009

DOI

10.1186/1753-6561-3-S7-S75

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