Molecular Biology Reports

, Volume 39, Issue 12, pp 10627–10635

Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis

  • Young Ho Lee
  • Sang-Cheol Bae
  • Sung Jae Choi
  • Jong Dae Ji
  • Gwan Gyu Song
Article

DOI: 10.1007/s11033-012-1952-x

Cite this article as:
Lee, Y.H., Bae, SC., Choi, S.J. et al. Mol Biol Rep (2012) 39: 10627. doi:10.1007/s11033-012-1952-x

Abstract

The aim of this study was to explore candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two SLE genome-wide association studies (GWASs) datasets were included in this study. Meta-analysis was conducted using 737,984 SNPs in 1,527 SLE cases and 3,421 controls of European ancestry, and 4,429 SNPs that met a threshold of p < 0.01 in a Korean RA GWAS dataset was used. ICSNPathway (identify candidate causal SNPs and pathways) analysis was applied to the meta-analysis results of the SLE GWAS datasets, and a RA GWAS dataset. The most significant result of SLE GWAS meta-analysis concerned rs2051549 in the human leukocyte antigen (HLA) region (p = 3.36E−22). In the non-HLA region, meta-analysis identified 6 SNPs associated with SLE with genome-wide significance (STAT4, TNPO3, BLK, FAM167A, and IRF5). ICSNPathway identified five candidate causal SNPs and 13 candidate causal pathways. This pathway-based analysis provides three hypotheses of the biological mechanism involved. First, rs8084 and rs7192 → HLA-DRA → bystander B cell activation. Second, rs1800629 → TNF → cytokine network. Third, rs1150752 and rs185819 → TNXB → collagen metabolic process. ICSNPathway analysis identified three candidate causal non-HLA SNPs and four candidate causal pathways involving the PADI4, MTR, PADI2, and TPH2 genes of RA. We identified five candidate SNPs and thirteen pathways, involving bystander B cell activation, cytokine network, and collagen metabolic processing, which may contribute to SLE susceptibility, and we revealed candidate causal non-HLA SNPs, genes, and pathways of RA.

Keywords

Genome-wide association studies Meta-analysis Pathway-based analysis Systemic lupus erythematosus Rheumatoid arthritis 

Supplementary material

11033_2012_1952_MOESM1_ESM.doc (437 kb)
Supplementary material 1 (DOC 437 kb)

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Young Ho Lee
    • 1
  • Sang-Cheol Bae
    • 2
  • Sung Jae Choi
    • 1
  • Jong Dae Ji
    • 1
  • Gwan Gyu Song
    • 1
  1. 1.Division of Rheumatology, Department of Internal MedicineKorea University Anam Hospital, Korea University College of MedicineSeoulKorea
  2. 2.Division of Rheumatology, Department of Internal MedicineThe Hospital for Rheumatic Diseases, Hanyang University Medical CenterSeoulKorea

Personalised recommendations