Common variants at CD40 and other loci confer risk of rheumatoid arthritis
Copyright policy )Common variants at CD40 and other loci confer risk of rheumatoid arthritis
To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).
- University of California, Davis United States
- Massachusetts General Hospital United States
- National Institutes of Health United States
- Harvard University United States
- University of Salford United Kingdom
Genetic Linkage, Polymorphism, Single Nucleotide, genetics: Arthritis, Arthritis, Rheumatoid, genetics: Chromosomes, genetics: Antigens, CD40, Rheumatoid, CD40, Chromosomes, Human, Humans, Genetic Predisposition to Disease, genetics: Haplotypes, CD40 Antigens, genetics: Arthritis, Rheumatoid, genetics: Antigens, Genome, Genome, Human, genetics: Polymorphism, Single Nucleotide, Linkage (Genetics), genetics: Polymorphism, Chromosome Mapping, Single Nucleotide, genetics: Chromosomes, Human, genetics: Genetic Predisposition to Disease, Haplotypes, Case-Control Studies, Human
Genetic Linkage, Polymorphism, Single Nucleotide, genetics: Arthritis, Arthritis, Rheumatoid, genetics: Chromosomes, genetics: Antigens, CD40, Rheumatoid, CD40, Chromosomes, Human, Humans, Genetic Predisposition to Disease, genetics: Haplotypes, CD40 Antigens, genetics: Arthritis, Rheumatoid, genetics: Antigens, Genome, Genome, Human, genetics: Polymorphism, Single Nucleotide, Linkage (Genetics), genetics: Polymorphism, Chromosome Mapping, Single Nucleotide, genetics: Chromosomes, Human, genetics: Genetic Predisposition to Disease, Haplotypes, Case-Control Studies, Human
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).486 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!