Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis
- Authors
- Lee, Young Ho; Bae, Sang-Cheol; Choi, Sung Jae; Ji, Jong Dae; Song, Gwan Gyu
- Issue Date
- 12월-2012
- Publisher
- SPRINGER
- Keywords
- Genome-wide association studies; Meta-analysis; Pathway-based analysis; Systemic lupus erythematosus; Rheumatoid arthritis
- Citation
- MOLECULAR BIOLOGY REPORTS, v.39, no.12, pp.10627 - 10635
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR BIOLOGY REPORTS
- Volume
- 39
- Number
- 12
- Start Page
- 10627
- End Page
- 10635
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/106788
- DOI
- 10.1007/s11033-012-1952-x
- ISSN
- 0301-4851
- 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.
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