|(G;G)||1.4||Normal risk for rheumatoid arthritis|
|(G;T)||1.8||0.87 reduced risk for rheumatoid athritis|
|(T;T)||1.8||0.87 reduced risk for rheumatoid athritis|
The association between rs4810485 and RA was first identified through a genome-wide association study (GWAS) meta-analysis and two subsequent replication studies in patients with European ancestry [PMID 18794853]. This study looked at the major allele G versus the minor allele T in a meta-analysis of previous GWAS followed by two replication studies. In the GWAS meta-analysis, which had 3,393 cases and 12,460 controls, they found rs4810485 to be associated with RA with a p-value of 2.4x10-7 and an odds ratio of 0.83. Two replication studies looking at 31 loci in combined 3,929 cases and 5,807 controls found the position to be associated with the disease with a p-value of 0.0032 and an odds ratio of 0.91. Jointly, the meta-analysis and replication studies showed an association with a p-value of 8.2x10-9 surpassing a conservative level of significance for joint analysis and an odds ratio of 0.87, suggesting that the minor allele T gives a modest protective effect against RA.
The association with RA was confirmed in a targeted validation study in the United Kingdom with 3,962 cases and 3,531 control patients [PMID 19435719]. This study found rs4810485 to be associated with RA with a p-value of 2x10-4 and an odds ratio of 0.86. Since this was a targeted study looking at 4 specific loci, the p-value is significant. Again, the odds ratio suggests a modest protective affect for the minor allele T.
An additional study looked at this SNP and its association with RA in individuals of Korean ancestry [PMID 19180477]. This study found no association between rs4810485 and RA in patients with Korean ancestry. The targeted validation study looked at 5 SNPs associated with RA in Europeans in 1,113 Korean cases and 988 controls, and found a p-value of 0.39 and an odds ratio of 1.06, suggesting no association between the SNP and RA in Koreans. This case highlights the importance of accounting for ancestry when testing genome-wide associations.
[PMID 19644859] Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis
|Title||Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock|
|Odds Ratio||1.18 [1.11-1.25]|
[PMID 20498205] Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
[PMID 21645569] A CD40 and an NCOA5 gene polymorphism confer susceptibility to psoriasis in a Southern European population: A case-control study
[PMID 21914625] A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis
[PMID 22087016] CD40 gene polymorphisms confer risk of Behcet's disease but not of Vogt-Koyanagi-Harada syndrome in a Han Chinese population
[PMID 22645426] CD40 Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population
[PMID 19159017] STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma.
[PMID 19180477] Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations.
[PMID 19435719] Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study.
[PMID 19674979] Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis.
[PMID 20018027] Conditional analysis of the major histocompatibility complex in rheumatoid arthritis.
[PMID 20426808] AntEpiSeeker: detecting epistatic interactions for case-control studies using a two-stage ant colony optimization algorithm.
[PMID 20439292] Genetic variants in the prediction of rheumatoid arthritis.
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|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23166616] Study of Association of CD40-CD154 Gene Polymorphisms with Disease Susceptibility and Cardiovascular Risk in Spanish Rheumatoid Arthritis Patients
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