Particular HLA–DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis

Gorman, Jennifer D.; David-Vaudey, Eve; Pai, Madhukar; Lum, Raymond F.; Criswell, Lindsey A.

doi:10.1002/art.20588

Cited by 73 publications

(49 citation statements)

References 32 publications

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“…The association of candidate genes -such as HLA-DRB1 and PTPN22 -with RA has been well replicated in previous genetic association studies [24,25] . To evaluate the accuracy of the prediction models, we split the entire dataset into a learning set and a validation set, with a 2: 1 ratio.…”

Section: Predictive Genetic Tests For Rasupporting

confidence: 52%

A Non-Parametric Method for Building Predictive Genetic Tests on High-Dimensional Data

Cui

Wei³

et al. 2011

Hum Hered

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Objective: Predictive tests that capitalize on emerging genetic findings hold great promise for enhanced personalized healthcare. With the emergence of a large amount of data from genome-wide association studies (GWAS), interest has shifted towards high-dimensional risk prediction.Methods: To form predictive genetic tests on high-dimensional data, we propose a non-parametric method, called the ‘forward ROC method’. The method adopts a computationally efficient algorithm to search for environment risk factors, genetic predictors on the entire genome, and their possible interactions for an optimal risk prediction model, without relying on prior knowledge of known risk factors. An efficient yet powerful procedure is also incorporated into the method to handle missing data. Results:Through simulations and real data applications, we found our proposed method outperformed the existing approaches. We applied the new method to the Wellcome Trust rheumatoid arthritis GWAS dataset with a total of 460,547 markers. The results from the risk prediction analysis suggested important roles of HLA-DRB1 and PTPN22 in predicting rheumatoid arthritis. Conclusion: We proposed a powerful and robust approach for high-dimensional risk prediction. The new method will facilitate future risk prediction that considers a large number of predictors and their interaction for improved performance.

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Section: Predictive Genetic Tests For Rasupporting

confidence: 52%

A Non-Parametric Method for Building Predictive Genetic Tests on High-Dimensional Data

Cui

Wei³

et al. 2011

Hum Hered

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“…Several studies have shown an association between the HLA-DRB1 gene and extraarticular manifestations of RA 2,3 . We analyzed the effect of the HLA-DRB1 gene and cytokine gene polymorphisms on the association of pulmonary fibrosis in Japanese patients with RA.…”

Section: To the Editormentioning

confidence: 99%

HLA-DRB1 Alleles and Rheumatoid Arthritis-related Pulmonary Fibrosis

Migita¹,

Nakamura²,

Koga³

et al. 2009

J Rheumatol

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“…18,19 Furthermore, dividing HLA-DRB1 QRRAA alleles into HLA-DRB1*04-QRRAA and HLA-DRB1*01-QRRAA subgroups, a per-allele hierarchy of risk was observed: *0401-QKRAA4*0404-QRRAA4 *0101-QRRAA4*1001-RRRAA. 20 Compound heterozygosity (*0401/*0404 heterozygosity) has been associated with a maximal genotypic risk for RA susceptibility and severity, [21][22][23][24][25] including vasculitis 26 and cardiovascular mortality. 27 It has also been proposed that certain HLA-DRB1 alleles protect against development of RA, compared with other HLA-DRB1 non-SE alleles.…”

Section: Introductionmentioning

confidence: 99%

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

et al. 2011

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Previously-proposed rheumatoid arthritis (RA) HLA-DRB1 susceptibility and protective models were compared, based on amino acids at positions 67-74 and autoantibody combinations. 3 657 RA patients and 1 357 controls were studied using logistic regression, with secondary stratification by anti-citrullinated peptide antibodies(ACPA) and rheumatoid factor(RF). Susceptibility models were based on previously defined HLA-DRB1 shared epitope(SE) subgroups. 70 DERAA 74 , D 70 and I 67 protective models were compared, adjusting for HLA-DRB1 SE. A hierarchy of risk was observed within the HLA-DRB1 SE, particularly for ACPA-positive and RF-positive RA: HLA-DRB1*0401B*04044*0101B*1001 (*04044*0101: P ¼ 0.0003). HLA-DRB1*0401/*0404 compound heterozygosity conferred a risk similar to *0401 homozygosity (P ¼ 0.70). Protective effects of D 70 and I 67 were similar. Predictions of the D 70 model fitted the data better than those of the I 67 model. The protective effect of D 70 showed a gene-dose effect (OR 0.82, 95% CI 0.73-0.92, P ¼ 5.8 Â 10 À4 ), but was only seen in RA patients positive for RF or ACPA. HLA-DRB1 SE alleles were also associated with ACPA-negative, RF-positive RA (OR 1.42 (1.15-1.76), P ¼ 0.0012).In conclusion, HLA-DRB1 SE alleles show heterogeneity in RA susceptibility; their major effect appears to be mediated by ACPA positivity, but a significant association of HLA-DRB1 SE with RF-positive, ACPA-negative RA was also observed. D 70 specifically protected against antibody-positive RA.

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Particular HLA–DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis

Cited by 73 publications

References 32 publications

A Non-Parametric Method for Building Predictive Genetic Tests on High-Dimensional Data

A Non-Parametric Method for Building Predictive Genetic Tests on High-Dimensional Data

HLA-DRB1 Alleles and Rheumatoid Arthritis-related Pulmonary Fibrosis

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

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