Allelic based gene-gene interactions in rheumatoid arthritis

被引：13
作者：
Jeesun Jung
Joon Jin Song
Deukwoo Kwon
机构：
[1] Indiana University School of Medicine,Department of Medical and Molecular Genetics
[2] University of Arkansas,Department of Mathematical Sciences
[3] National Cancer Institute,Division of Cancer Epidemiology and Genetics
来源：
BMC Proceedings | / 3卷 / Suppl 7期
关键词：
Rheumatoid Arthritis; Linkage Disequilibrium; Migration Inhibitory Factor; Multifactor Dimensionality Reduction; Allelic Combination;
D O I：
10.1186/1753-6561-3-S7-S76
中图分类号：
学科分类号：
摘要：
The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel method that can detect the interaction by a definition of nonrandom association of alleles that occurs when the contribution to RA of a particular allele inherited in one gene depends on a particular allele inherited at other unlinked genes. Starting with 639 single-nucleotide polymorphisms (SNPs) from 26 candidate genes, we identified ten two-way interacting genes and one case of three-way interacting genes. SNP rs2476601 on PTPN22 interacts with rs2306772 on SLC22A4, which interacts with rs881372 on TRAF1 and rs2900180 on C5, respectively. SNP rs2900180 on C5 interacts with rs2242720 on RUNX1, which interacts with rs881375 on TRAF1. Furthermore, rs2476601 on PTPN22 also interacts with three SNPs (rs2905325, rs1476482, and rs2106549) in linkage disequilibrium (LD) on IL6. The other three SNPs (rs2961280, rs2961283, and rs2905308) in LD on IL6 interact with two SNPs (rs477515 and rs2516049) on HLA-DRB1. SNPs rs660895 and rs532098 on HLA-DRB1 interact with rs2834779 and four SNPs in LD on RUNX1. Three-way interacting genes of rs10229203 on IL6, rs4816502 on RUNX1, and rs10818500 on C5 were also detected.
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共 75 条
[1]  
Dieudo P(2005)Genetic basis of rheumatoid arthritis Joint Bone Spine 72 520-526
[2]  
Gornelis F(2009)Allelic based gene-gene interaction association with quantitative traits Genet Epidemiol 33 332-343
[3]  
Jung J(2007)Gene-gene and gene-environment interactions involving Am J Hum Genet 80 867-875
[4]  
Sun B(1999), Arthritis Rheum 42 438-442
[5]  
Kwon D(2007), and smoking in two subsets of rheumatoid arthritis BMC Proc 1 S17-10
[6]  
Koller DL(2007)Tumor necrosis factor a microsatellite polymorphism is associated with rheumatoid arthritis severity through an interaction with the HLA-DRB1 shared epitope BMC Proc 1 S13-1208
[7]  
Foroud TM(2006)Evaluating gene × gene and gene × smoking interaction in rheumatoid arthritis using candidate genes in GAW 15 Genes Immun 7 1-35
[8]  
Kallberg H(2007)Constructing gene association networks for rheumatoid arthritis using the backward genotype-trait association (BGTA) algorithm N Engl J Med 357 1199-411
[9]  
Padyukov L(1972)Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits Biometrika 59 19-386
[10]  
Plenge RM(1979)TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study Biometrika 66 403-288
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