Additional file 2: Figure S1. of Gene Set Enrichment Analyses: lessons learned from the heart failure phenotype

Overlapping genes among significant pathways for hearf failure before data processing. (PDF 145 kb

Effect size of differentially expressed BP genes in the Framingham Heart Study and the Illumina cohorts.

<p>A) SBP; B) DBP; C) HTN. The x-axis is the effect size of the differentially expressed genes in the FHS cohort and the y-axis is the effect size in the Illumina cohorts. The BP signature genes identified both in the FHS and the Illumina cohorts at <i>p</i><0.05 (Bonferroni corrected) are highlighted. <i>pi1</i> values indicate the proportion of significant signals among the tested associations [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref011" target="_blank">11</a>] (See details in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#sec009" target="_blank">Methods</a> section).</p

Gene set enrichment analysis for BP associated gene expression changes.

<p>*<b>NES</b>: normalized enrichment score;</p><p><b>GO-BP</b>: Gene ontology- biological process;</p><p><b>KEGG</b>: Kyoto encyclopedia of genes and genomes.</p><p>Gene set enrichment analysis for BP associated gene expression changes.</p

GWAS eQTLs for the top differentially expressed BP signature genes.

<p>* rs653178, intronic to <i>ATXN2</i> and in tight linkage disequilibrium with rs3184504 (r² = 1), was also associated with BP in ICBP GWAS and all the 6 genes;</p><p>⁺ A proxy SNP rs4698412 at LD r² = 1 associated with the same trait;</p><p>$ A proxy SNP rs4389526 at LD r² = 1 associated with the same trait;</p><p>^§ indicated eQTL were identified from[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref012" target="_blank">12</a>].</p><p>^& highlighted p values indicated passing transcriptome-wide significance at Bonferroni corrected <i>p</i><0</p><p>GWAS eQTLs for the top differentially expressed BP signature genes.</p

Clinical characteristics of the study cohorts.

<p>Clinical characteristics of the study cohorts.</p

Global view of BP eQTLs effects on differentially expressed BP signature genes.

<p>A) 2-Dimensional plot of in whole blood eQTLs vs. transcript position genome wide. eQTL-transcript pairs at FDR<0.1 are shown in black dots; those that fall along the diagonal are cis eQTLs and all others are trans eQTLS. eQTL-transcript pair SNPs that are associated with BP in GWAS [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref003" target="_blank">3</a>] are highlighted with blue triangles. eQTL-transcript pair genes that are BP signature genes from analysis of differential gene expression in relation to BP are depicted by red circles. B) Regional association plots for rs3184504 proxy QTLs that showing association with BP in ICBP GWAS [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref003" target="_blank">3</a>]. −log10(p) indicated the −log10 transformed DBP association <i>p</i> values in ICBP GWAS [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref003" target="_blank">3</a>]. Color coding indicates the strength (measured by r²) of LD of each SNP with the top SNP (rs3184504). Five master <i>trans-</i>eQTLs (also BP GWAS SNPs) for BP signature genes are labeled in the figure. This figure was drawn by LocusZoom [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005035#pgen.1005035.ref032" target="_blank">32</a>].</p

Differentially expressed genes associated with BP and hypertension at Bonferroni correction <i>p</i><0.05 in meta-analysis of the six cohorts.

<p>*<b>Meta</b>: meta-analysis of all six cohorts.</p><p>Differentially expressed genes associated with BP and hypertension at Bonferroni correction <i>p</i><0.05 in meta-analysis of the six cohorts.</p