Dataset Information

Genome-wide gene-based analysis of rheumatoid arthritis-associated interaction with PTPN22 and HLA-DRB1.

ABSTRACT: The genes PTPN22 and HLA-DRB1 have been found by a number of studies to confer an increased risk for rheumatoid arthritis (RA), which indicates that both genes play an important role in RA etiology. It is believed that they not only have strong association with RA individually, but also interact with other related genes that have not been found to have predisposing RA mutations. In this paper, we conduct genome-wide searches for RA-associated gene-gene interactions that involve PTPN22 or HLA-DRB1 using the Genetic Analysis Workshop 16 Problem 1 data from the North American Rheumatoid Arthritis Consortium. MGC13017, HSPCAL3, MIA, PTPNS1L, and IGLVI-70, which showed association with RA in previous studies, have been confirmed in our analysis.

SUBMITTER: Qiao B

PROVIDER: S-EPMC2795906 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide gene-based analysis of rheumatoid arthritis-associated interaction with PTPN22 and HLA-DRB1.

Qiao Bo B Huang Chien Hsun CH Cong Lei L Xie Jun J Lo Shaw-Hwa SH Zheng Tian T

BMC proceedings 20091215

The genes PTPN22 and HLA-DRB1 have been found by a number of studies to confer an increased risk for rheumatoid arthritis (RA), which indicates that both genes play an important role in RA etiology. It is believed that they not only have strong association with RA individually, but also interact with other related genes that have not been found to have predisposing RA mutations. In this paper, we conduct genome-wide searches for RA-associated gene-gene interactions that involve PTPN22 or HLA-DRB ...[more]

PMID: 20017999

Similar Datasets

Project description:INTRODUCTION: Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04. METHODS: We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen. RESULTS: Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P?=?0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P?=?0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P?=?0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P?=?0.02). CONCLUSION: These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.

Dataset Information

Genome-wide gene-based analysis of rheumatoid arthritis-associated interaction with PTPN22 and HLA-DRB1.

Publications

Genome-wide gene-based analysis of rheumatoid arthritis-associated interaction with PTPN22 and HLA-DRB1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets