Genome‐wide association study of rheumatoid arthritis in Koreans: Population‐specific loci as well as overlap with European susceptibility loci

Freudenberg, Jan; Lee, Hye‐Soon; Han, Bok‐Ghee; Shin, Hyoung-Doo; Kang, Young Mo; Sung, Yoon‐Kyoung; Shim, Seung Cheol; Choi, Chan-Bum; Lee, Annette T.; Gregersen, Peter K.; Bae, Sang Cheol

doi:10.1002/art.30235

Cited by 125 publications

(109 citation statements)

References 26 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Recent genome-wide association analyses have revealed an association of the PTPN2 locus with RA and JIA (8)(9)(10)(11). In this study, we investigated the effect of TC-PTP deficiency on mouse bone and joint tissues, in light of these studies.…”

Section: Discussionmentioning

confidence: 99%

T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice

Doody¹,

Bussières-Marmen²,

Li³

et al. 2012

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. T cell protein tyrosine phosphatase (TC-PTP) is an important regulator of hematopoiesis and cytokine signaling. Recently, several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in the locus of TC-PTP that are associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other autoimmune diseases. The aim of this study was to evaluate the effect of TC-PTP deficiency on the bone and joint environment using a knockout mouse model.Methods. Radiographic and micro-computed tomography analyses were performed on femurs of 3-week-old mice. In addition, the femorotibial joints were assessed by histology, flow cytometry, and cytokine detection.Results. Deficiency of TC-PTP resulted in decreased bone volume as well as an increase in osteoclast density within the mouse femurs. In addition, synovitis, characterized by infiltration of mixed inflammatory cell types and proinflammatory cytokines, developed in the knee joints of TC-PTP ؊/؊ mice.Conclusion. These findings demonstrate that loss of TC-PTP expression results in synovitis with several hallmarks of inflammatory arthritis. The inflammatory environment observed in the knee joints of TC-PTP ؊/؊ mice differs from the systemic inflammation previously described in these mice and merits further research into the role of TC-PTP in the synovium. Furthermore, the results support recently described associations between SNPs in the TC-PTP locus and arthritis incidence.

show abstract

Section: Discussionmentioning

confidence: 99%

T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice

Doody¹,

Bussières-Marmen²,

Li³

et al. 2012

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Having demonstrated the accuracy of our imputation protocol, we imputed HLA alleles and tested them for association in two RA GWAS and one RA Immunochip datasets of Asian ancestries (a GWAS including 466 ACPA-positive RA cases and 873 controls from China (18); a GWAS including 799 ACPA-positive RA cases and 751 controls from South Korea (19); an Immunochip study including 1517 ACPA-positive RA cases and 2691 controls from South Korea (20); in total, 2782 ACPA-positive RA cases and 4315 controls). We adopted the pan-Asian imputation reference panel due to its reliable imputation accuracy on HLA-DRB1 alleles and similar genetic backgrounds to the subjects in the Asian RA GWAS, while we note that the following association analysis results did not change substantially when we adopted the large-scaled European reference panel or the combined panel of Europeans and Asians.…”

Section: Risk Of Hla-drb1 Variants In the Asian Ra Samplesmentioning

confidence: 99%

“…We used data from two GWAS and one Immunochip study from the Asian populations for 2782 cases and 4315 controls: one GWAS with the samples from China (466 cases and 873 controls) (18), one GWAS with the samples from South Korea (799 cases and 751 controls) (19) and one Immunochip study with the samples from South Korea (1517 cases and 2691 controls) (20). All cases met the 1987 American College of Rheumatology diagnostic criteria (30) and were confirmed to be ACPA positive.…”

Section: Ra Gwas Data In Asian Populationsmentioning

confidence: 99%

“…Details of the GWAS and Immunochip data, including genotyping platforms, were described elsewhere (18)(19)(20). Each dataset was filtered with the stringent QC criteria as described elsewhere (18,19,31), including SNP and sample call rate cutoffs, exclusion of closely related relative and outliers in terms of ancestry, and SNP minor allele frequency (MAF) and Hardy -Weinberg equilibrium cutoffs.…”

Section: Ra Gwas Data In Asian Populationsmentioning

confidence: 99%

See 1 more Smart Citation

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

Okada

Kim

Han

et al. 2014

Human Molecular Genetics

Self Cite

143

164

View full text Add to dashboard Cite

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRb1 at amino acid position 13, located outside the classical shared epitope (P omnibus 5 6.9 3 10 2135 ). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr Gly > Ser)-but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional P omnibus 5 2.2 3 10 233) and 74 (conditional P omnibus 5 1.1 3 10 28). Outside of HLA-DRb1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P 5 3.8 3 10 26) and HLA-DPb1 (Phe9, conditional P 5 3.0 3 10 25 ) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino † These authors jointly directed this project.

show abstract

“…Several genome-wide association studies (GWAS) have been undertaken to investigate the genetic basis of rheumatoid arthritis (RA) (1)(2)(3)(4)(5)(6)(7). These studies have been recently combined into a transcontinental metaanalysis (8), which most comprehensively evaluates the influence of common single nucleotide variants on RA susceptibility in populations with European and Asian ancestry.…”

Section: Introductionmentioning

confidence: 99%

Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer Regions

Freudenberg

Gregersen

2015

Mol Med

Self Cite

View full text Add to dashboard Cite

Genome‐wide association study of rheumatoid arthritis in Koreans: Population‐specific loci as well as overlap with European susceptibility loci

Cited by 125 publications

References 26 publications

T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice

T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer Regions

Contact Info

Product

Resources

About