Significantly associated SNPs of the 6 top genes.

<p>SNP, single nucleotide polymorphism; Chr, chromosome; bp, base pair; MAF, minor allele frequency in control group; OR, odds ratio. The imputation quality indicates the average posterior probability for the most likely genotype generated by MACH, ranging from 0–1.</p

Q-Q plot for the GWAS after imputation on clinical restenosis in the GENDER study population. Lambda = 1.027.

<p>Q-Q plot for the GWAS after imputation on clinical restenosis in the GENDER study population. Lambda  = 1.027.</p

Pathway Analysis Using Genome-Wide Association Study Data for Coronary Restenosis – A Potential Role for the PARVB Gene

<div><p>Background</p><p>Coronary restenosis after percutaneous coronary intervention (PCI) still remains a significant limitation of the procedure. The causative mechanisms of restenosis have not yet been fully identified. The goal of the current study was to perform gene-set analysis of biological pathways related to inflammation, proliferation, vascular function and transcriptional regulation on coronary restenosis to identify novel genes and pathways related to this condition.</p><p>Methods</p><p>The GENetic DEterminants of Restenosis (GENDER) databank contains genotypic data of 556,099SNPs of 295 cases with restenosis and 571 matched controls. Fifty-four pathways, related to known restenosis-related processes, were selected. Gene-set analysis was performed using PLINK, GRASS and ALIGATOR software. Pathways with a p<0.01 were fine-mapped and significantly associated SNPs were analyzed in an independent replication cohort.</p><p>Results</p><p>Six pathways (cell-extracellular matrix (ECM) interactions pathway, IL2 signaling pathway, IL6 signaling pathway, platelet derived growth factor pathway, vitamin D receptor pathway and the mitochondria pathway) were significantly associated in one or two of the software packages. Two SNPs in the cell-ECM interactions pathway were replicated in an independent restenosis cohort. No replication was obtained for the other pathways.</p><p>Conclusion</p><p>With these results we demonstrate a potential role of the cell-ECM interactions pathway in the development of coronary restenosis. These findings contribute to the increasing knowledge of the genetic etiology of restenosis formation and could serve as a hypothesis-generating effort for further functional studies.</p></div

Pathways associated with restenosis with PLINK or GRASS.

<p>A complete overview of all pathways can be found in Supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070676#pone.0070676.s001" target="_blank">Table S1</a>. NS, not significant (pathway did not meet test criteria).</p