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Journal ArticleDOI

A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.

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TLDR
The results suggest that CCR6 is critically involved in IL-17–driven autoimmunity in human diseases, and is associated with susceptibility to Graves' and Crohn's diseases.
Abstract
Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here, through a genome-wide association study of rheumatoid arthritis, we identified a polymorphism in CCR6, the gene encoding chemokine (C-C motif) receptor 6 (a surface marker for Th17 cells) at 6q27, that was associated with rheumatoid arthritis susceptibility and was validated in two independent replication cohorts from Japan (rs3093024, a total of 7,069 individuals with rheumatoid arthritis (cases) and 20,727 controls, overall odds ratio = 1.19, P = 7.7 x 10(-19)). We identified a triallelic dinucleotide polymorphism of CCR6 (CCR6DNP) in strong linkage disequilibrium with rs3093024 that showed effects on gene transcription. The CCR6DNP genotype was correlated with the expression level of CCR6 and was associated with the presence of interleukin-17 (IL-17) in the sera of subjects with rheumatoid arthritis. Moreover, CCR6DNP was associated with susceptibility to Graves' and Crohn's diseases. These results suggest that CCR6 is critically involved in IL-17-driven autoimmunity in human diseases.

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Citations
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Journal ArticleDOI

New IBD genetics: common pathways with other diseases

TL;DR: The presently available data on the genetic overlap between IBD and other diseases is detailed and it is anticipated that these genetic insights will transform the landscape of common complex diseases such as IBD.
Journal ArticleDOI

The IL-23-IL-17 axis in inflammatory arthritis

TL;DR: Blockade of IL-17 and/or TH17-cell activity in combination with anti-TNF therapy might be a successful approach to achieving stable remission or even prevention of chronic immune-mediated inflammatory diseases.
Journal ArticleDOI

Genetics and epigenetics of rheumatoid arthritis

TL;DR: The major advances in identifying RA genetic susceptibility markers both within and outside of the MHC are reviewed and current knowledge of the role of epigenetics in RA susceptibility is reviewed.
References
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Journal ArticleDOI

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
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Principal components analysis corrects for stratification in genome-wide association studies

TL;DR: This work describes a method that enables explicit detection and correction of population stratification on a genome-wide scale and uses principal components analysis to explicitly model ancestry differences between cases and controls.
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Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Paul Burton, +195 more
- 07 Jun 2007 - 
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI

Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages

TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI

A second generation human haplotype map of over 3.1 million SNPs

Kelly A. Frazer, +237 more
- 18 Oct 2007 - 
TL;DR: The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.
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