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Title: A protein network of common susceptibility genes provides a link in the genetic architecture of chronic inflammation and cardiovascular disease      
dateReleased:
09-01-2015
description:
Genome-wide association studies (GWAS) have identified hundreds of susceptibility loci for chronic and inflammatory disease phenotypes in humans. There is increasing evidence that chronic inflammation is a crucial driver in the pathogenesis of cardiovascular diseases (CVD), which may be genetically determined. To understand the genetic architecture underlying chronic inflammation and CVD we performed a systematic analysis of (1) common risk alleles coming from published GWAS, (2) of protein-protein interaction (PPI) networks informed by (3) gene expression data with a defined molecular target involved in the inflammatory processes promoting CVD, MRP8. (4) through analysis of integrated haplotype scores (iHS) and FST values in HapMap phase 2 data, we investigated whether recent selection pressure acting upon inflammatory genes affected CVD susceptibility loci. Our findings provide significant evidence for a PPI network, which connects inflammatory and cardiovascular susceptibility genes, and establish a genetic framework of inflammatory CVD. 41.59% of PPI genes are associated with immune functions. 28.3% of integrated genes can be linked to both, an inflammatory and cardiovascular disease phenotype. Interestingly, CDKN2B, and CELSR2/PSRC1/MYBPHL/SORT1, unequivocally replicated CVD loci, are integrated within this network as are several SNPs located in transcription factor recognition sequences, i.e. NFKB1, STAT3, which are key factors in inflammation. Finally, we observed a significant enrichment of inflammatory variants within CVD cluster loci that are targets of selection. Overall, 32 genes exhibit traces of selection, 16 of which are part of the PPI, further suggesting that recent selective sweeps may have affected the genomic architecture underlying CVD. 6 samples, no replicates.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-54989
refinement:
raw
alternateIdentifiers:
54989
keywords:
functional genomics
dateModified:
09-05-2015
creators:
Mona Riemenschneider
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-10558
name:
Illumina HumanHT-12 V4.0 expression beadchip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54989/E-GEOD-54989.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54989/E-GEOD-54989.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54989
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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