Constructing gene association networks for rheumatoid arthritis using the backward genotype-trait association (BGTA) algorithm
نویسندگان
چکیده
BACKGROUND Rheumatoid arthritis (RA, MIM 180300) is a common and complex inflammatory disorder. The North American Rheumatoid Arthritis Consortium (NARAC) data, as part of the Genetic Analysis Workshop 15 data, consists of both genome scan and candidate gene studies on RA patients. RESULTS We applied the backward genotype-trait association (BGTA) algorithm to capture marginal and gene x gene interaction effects of multiple susceptibility loci on RA disease status. A two-stage screening approach was used for the genome scan, whereas a comprehensive study of all possible subsets was conducted for the candidate genes. For the genome scan, we constructed an association network among 39 genetic loci that demonstrated strong signals, 19 of which have been reported in the RA literature. For the candidate genes, we found strong signals for PTPN22 and SUMO4. Based on significant association evidence, we built an association network among the loci of PTPN22, PADI4, DLG5, SLC22A4, SUMO4, and CARD15. To control for false positives, we used permutation tests to constrain the family-wise type I error rate to 1%. CONCLUSION Using the BGTA algorithm, we identified genetic loci and candidate genes that were associated with RA susceptibility and association networks among them. For the first time, we report possible interactions between single-nucleotide polymorphisms/genes, which may be useful for biological interpretation.
منابع مشابه
Constructing Association Network in Two-Stage Analysis: An application of Backward Genotype-Trait Association (BGTA) Algorithm to NARAC Data
In this paper, we applied the Backward Genotype-Trait Association (BGTA) algorithm to capture both the marginal and gene-gene interaction effects of multiple susceptibility loci on the Rheumatoid Arthritis (RA) disease, using the dataset ascertained by North American Rheumatoid Arthritis Consortium (NARAC) and provided as part of the GAW15 datasets. We proposed a two-stage analysis of whole-gen...
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ورودعنوان ژورنال:
- BMC Proceedings
دوره 1 شماره
صفحات -
تاریخ انتشار 2007