ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2267

Genome-Wide Pathway Analysis of Genome-Wide Association Studies On Systemic Lupus Erythematosus

Young Ho Lee1, Sung Jae Choi2, Jong Dae Ji2 and Gwan Gyu Song3, 1Internal Medicine, Rheumatology, Korea University Medical Center, Seoul, South Korea, 2Rheumatology, Korea University Medical Center, Seoul, South Korea, 3Div of Rheum, Dept of Int Med, Korea Univ College of Med, Seoul, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Genome-wide association studies (GWASs) have been successfully used to identify novel common genetic variants that contribute to susceptibility to complex diseases, but individual GWASs are limited in terms of identifying new loci. Thus, pathway-based analysis is required to identify further new loci that contribute to susceptibility to complex diseases. The aim of this study was to explore candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms of systemic lupus erythematosus (SLE).

Methods:

Two SLE 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 after quality control filtering, and ICSNPathway (identify candidate causal SNPs and pathways) analysis was applied to the meta-analysis results of the SLE GWAS datasets.

Results:

The most significant result of SLE GWAS meta-analysis concerned rs2051549 in the human leukocyte antigen (HLA) region (p = 3.36E-22). In addition, 103 SNPs had observed p-values of less than 5 × 10-8 (genome-wide significance). 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 à HLA-DRA à bystander B cell activation. Second, rs1800629 à TNF à cytokine network. Third, rs1150752 and rs185819 à TNXB à collagen metabolic process.

Conclusion:

By applying ICSNPathway to the meta-analysis results of two SLE GWAS datasets, 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.

Disclosure:

Y. H. Lee,
None;

S. J. Choi,
None;

J. D. Ji,
None;

G. G. Song,
None.

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