Genome-wide haplotype association analysis and gene prioritization identify CCL3 as a risk locus for rheumatoid arthritis.
Rheumatoid arthritis (RA) is a common autoimmune disease caused by a complex interaction of multiple genetic variants and environmental factors. The association between RA and genetic susceptibility loci has been observed in many different populations, and most studies have focused on univariate analyses of single nucleotide polymorphisms. We performed a genome-wide haplotype association study and prioritized RA-related genes within 100 kb in either direction of significant haplotypes (P < 0.0001), based on their similarity to known RA susceptibility genes. The results showed that the chemokine CCL3 was associated with susceptibility to RA. A haplotype that located CCL3 on chromosome 17q12 had significant correlation with RA (P = 7.56E-05), and the global similarity score of CCL3 was ranked in the top of all RA-related genes, excluding known susceptibility genes (P = 8.42E-07). Our findings provide further evidence for the potential importance of the chemokine CCL3 in RA, and will facilitate the further understanding of its role in immunological regulation and the pathogenesis of RA.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. zhangruijie2009@yahoo.com.cn
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D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D054405:Chemokine CCL3 / Q000235:genetics*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012217:Rheumatoid Factor / Q000276:immunology; D012306:Risk; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D001324:Autoantigens; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor