PMID- 23053960
OWN - NLM
STAT- MEDLINE
DCOM- 20130409
LR  - 20211021
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 39
IP  - 12
DP  - 2012 Dec
TI  - Genome-wide pathway analysis of genome-wide association studies on systemic lupus 
      erythematosus and rheumatoid arthritis.
PG  - 10627-35
LID - 10.1007/s11033-012-1952-x [doi]
AB  - 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.
FAU - Lee, Young Ho
AU  - Lee YH
AD  - Division of Rheumatology, Department of Internal Medicine, Korea University Anam 
      Hospital, Korea University College of Medicine, 126-1, 5-ga, Anam-dong, 
      Seongbuk-gu, Seoul, 136-705, Korea. lyhcgh@korea.ac.kr
FAU - Bae, Sang-Cheol
AU  - Bae SC
FAU - Choi, Sung Jae
AU  - Choi SJ
FAU - Ji, Jong Dae
AU  - Ji JD
FAU - Song, Gwan Gyu
AU  - Song GG
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20121007
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Arthritis, Rheumatoid/*genetics/immunology
MH  - Databases, Genetic
MH  - *Genetic Predisposition to Disease
MH  - *Genome-Wide Association Study
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Linkage Disequilibrium/genetics
MH  - Lupus Erythematosus, Systemic/*genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Signal Transduction/*genetics
EDAT- 2012/10/12 06:00
MHDA- 2013/04/10 06:00
CRDT- 2012/10/12 06:00
PHST- 2011/12/08 00:00 [received]
PHST- 2012/10/01 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/04/10 06:00 [medline]
AID - 10.1007/s11033-012-1952-x [doi]
PST - ppublish
SO  - Mol Biol Rep. 2012 Dec;39(12):10627-35. doi: 10.1007/s11033-012-1952-x. Epub 2012 
      Oct 7.