HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort

Orozco, Gisela; Barton, Anne; Eyre, Steve; Ding, Bo; Worthington, Jane; Ke, Xiayi; Thomson, Wendy

doi:10.1038/gene.2010.57

Cited by 16 publications

(11 citation statements)

References 40 publications

(43 reference statements)

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“…The most associated SNP in this region is rs3117213, located between the pseudogenes HLA-DPA2 and COL11A2P . This SNP has previously shown association with ACPA-positive rheumatoid arthritis (RA) in northern European cohorts and is independent of the known RA HLA-DRB1 risk alleles 29 30. The association of HLA-DPB1 alleles with chronic beryllium disease is well established 31.…”

Section: Discussionmentioning

confidence: 92%

Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

et al. 2012

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ObjectivesSystemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype.MethodsA high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined.ResultsUsing this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon.ConclusionThese data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis.

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Section: Discussionmentioning

confidence: 92%

Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

et al. 2012

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“…There are about 31 pairs involving SNP rs2107191 displaying a recessive-interference pattern (M2) [13]. The SNP rs2107191 is located very closely with gene OR2H1, which has been reported as a susceptibility locus for RA [18]. The bottom panel of Figure 6 provides all identified compositional epistasis patterns in RA.…”

Section: Resultsmentioning

confidence: 99%

The complete compositional epistasis detection in genome-wide association studies

Wan

Yang

et al. 2013

BMC Genet

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BackgroundThe detection of epistasis among genetic markers is of great interest in genome-wide association studies (GWAS). In recent years, much research has been devoted to find disease-associated epistasis in GWAS. However, due to the high computational cost involved, most methods focus on specific epistasis models, making the potential loss of power when the underlying epistasis models are not examined in these analyses.ResultsIn this work, we propose a computational efficient approach based on complete enumeration of two-locus epistasis models. This approach uses a two-stage (screening and testing) search strategy and guarantees the enumeration of all epistasis patterns. The implementation is done on graphic processing units (GPU), which can finish the analysis on a GWAS data (with around 5,000 subjects and around 350,000 markers) within two hours. Source code is available at http://bioinformatics.ust.hk/BOOST.htmlâˆ–#GBOOST.ConclusionsThis work demonstrates that the complete compositional epistasis detection is computationally feasible in GWAS.

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“…HLA‐DPB1 , one of the classical gene that lies in cetromeric side of HLA‐class II region, and previous studies have indicated its significant associations with many diseases, such as rheumatoid arthritis, multiple sclerosis, Graves’ disease, bipolar disorder, and graft‐versus‐host disease (GVHD) . Furthermore in 2009, Kamatani et al identifies variants in the HLA‐DP locus associated with chronic hepatitis B in Asians and many following studies have showed its influence to disease progression or hepatocellular carcinoma .…”

Section: Discussionmentioning

confidence: 99%

Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C

Hiramatsu

Matsuda

Nemoto

et al. 2017

Journal of Medical Virology

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Recent genome-wide studies have demonstrated that HLA class II gene may play an important role in viral hepatitis. We studied genetic polymorphism and RNA expression of HLA class II genes in HCV-related liver diseases. The study was performed in groups consisting of 24 patients with HCV-related liver disease (12 of persistent normal ALT: PNALT group and 12 of advanced liver disease: ALD group) and 26 patients without HCV infection (control group). In PBMC samples, RNA expression of HLA class II genes (HLA-DPA1, DPB1, DQA1, DQB1, and DRB1) was analyzed by real-time RT-PCR. Furthermore, 22 single nucleotide polymorphisms (SNPs) in HLA class II gene and two SNPs in IL28B gene were genotyped by genetic analyzer (GENECUBE®). In expression analysis, only DPB1 level was significantly different. Mean expression level of DPB1gene in control group was 160.0, PNALT group 233.8, and ALD group 465.0 (P < 0.01). Of 24 SNPs, allele frequencies were statistically different in two SNPs (rs2071025 and rs3116996) between PNALT groups and ALD group (P < 0.01). In rs2071025, TT genotype was frequently detected in ALD group and expression level was significantly higher than the other genotypes (449.2 vs 312.9, P < 0.01). In rs3116996, TA or TT (non AA) genotype was frequently detected in ALD group and expression level was significantly higher than genotype AA (457.1 vs 220.9, P < 0.01). Genotyping and expression analysis in HLA class II gene revealed that two SNPs of HLA-DPB1 (rs2071025 and rs3116996) were significantly correlated to RNA expression and progression of HCV-related liver diseases.

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HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort

Cited by 16 publications

References 40 publications

Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

The complete compositional epistasis detection in genome-wide association studies

Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C

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