Schematic description of the association model used to quantify the overlap between regulatory elements (black and red DHS peaks) and disease-associated variants (SNP1, 2 and 3) in various cell types (cell type 1, 2 and 3).

<p>The model estimates the regulatory activity by counting the number of DHS peaks (red) located within the region of a 500kb with the associated tag SNP in the middle.</p

Tissues and cell types associated with common variants identified by selected GWASs.

<p>Each point represents the separate replicate of DHS assay in the given tissue.</p

Systematic association of common variants identified by 94 different GWAS with open chromatin (DHS) in selected tissues and cells.

<p>The individual GWAS are sorted based on the minimal association p-value with 466 DHS (only selected DHS samples are shown). Size of the dot represents the enrichment over the null distribution and color of the dot represents the significance of the enrichment—with black being the most significant. The bar graphs depict the number of associated SNPs (grey), the fraction of coding SNPs (red) and minor allele frequency (green). Heatmap depicts the distribution of SNPs with respect to transcriptional start sites (intensity of blue depicts the fraction of SNPs within the distance bin). Green/orange/white bar shows the presence of the replication cohort (green—present, white—no replication cohort as specified in the in NHGRI GWAS Catalog) separately for each GWAS. Group bar depicts the annotation of GWAS to one of three “GWAS groups”. Green—GWAS with the best association p-value < = 0.0001, orange < = 0.01 and red—GWAS with the best association p-value < 0.01.</p

Comparison of selected GWAS parameter between three GWAS groups.

<p>A) The number of associated SNPs B) the fraction of coding SNPs C) minor allele frequency and D) the distribution of SNPs with respect to transcriptional start sites (no line—non significant, * p-value < 0.05, ** p-value < 0.01, using Wilcoxon signed-rank test), green—GWAS with the best association p-value < = 0.0001, orange < = 0.01 and red—GWAS with the best association p-value < 0.01.</p

Additional file 5: Table S6. of Systematic analysis of chromatin interactions at disease associated loci links novel candidate genes to inflammatory bowel disease

Upstream regulators. (XLSX 135 kb

Additional file 7: Table S3. of Systematic analysis of chromatin interactions at disease associated loci links novel candidate genes to inflammatory bowel disease

Publicly available datasets. (XLSX 11 kb

Overview of methodology.

<p>LV, left ventricle; RV, right ventricle; Ant., anterior; Post., posterior. <b>A,</b> gross showing a transverse heart slice of arrhythmogenic cardiomyopathy. <b>B,</b> transverse slice dissection scheme. <b>C</b>–<b>F,</b> examples of digital slide processing. Regions of interest are shown in orange lines (defining the epicardium, compact myocardium divided by an equidistant midline and trabeculated part). <b>C,</b> slide from the left ventricle posterior wall. <b>D,</b> slide C after digital processing. Red: cardiomyocytes. Blue: connective tissue. Pseudo green: adipose tissue. <b>E,</b> slide from the right ventricle lateral wall. <b>F,</b> slide E after digital processing. Red: cardiomyocytes. Blue: connective tissue. Pseudo green: adipose tissue.</p

Schematic overview of fibrosis and adipose tissue in heart slices of control hearts.

<p>The results of the digital quantification in percentage of fibrosis or adipose tissue are shown using a color scale. The epicardial region has been excluded from the analysis. LV, left ventricle; RV, right ventricle; Ant., anterior; Post., posterior</p

Schematic heart slice overview of patients with a clinical phenotype of dilated cardiomyopathy.

<p>The results of the digital quantification in heart slices in percentage of fibrosis or adipose tissue are shown using a color scale. The epicardial region has been excluded from this overview. LV, left ventricle; RV, right ventricle; Ant., anterior; Post., posterior</p

Patient characteristics of the <i>PLN</i> p.Arg14del mutation carriers.

<p>SD, standard deviation; ICD, implantable cardioverter-defibrillator; CRT-D, cardiac resynchronization therapy defibrillator.</p