Journal: Genome Biology

Article Title: Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

doi: 10.1186/s13059-021-02560-3

Figure Lengend Snippet: GWAS enrichments for immune cell H3K4me1 broadPeaks from consolidated Roadmap Epigenomics consortium data: shown are significant cell type-specific enrichment results ( q value < 0.01, BH correction) for FORGE2 analysis across the NHGRI/EBI GWAS catalogue (downloaded 2 September 2019). GWAS phenotypes (rows) are clustered using complete linkage clustering (Euclidean distance), while different tissues and cell types (columns) are grouped according to related tissue or cell type categories (e.g. T cell categories are placed together, as are haematopoietic stem cell categories, etc.). All sample categories, including non-immune cell categories, are shown. Values are row-normalised, with reference lineplot on the left indicating top enrichment value for each category. Clustering reveals grouping of related phenotypes with similar immune cell type-specific enrichment profiles. We highlighted several groups including known related phenotypes such as mean corpuscular volume for HSCs, monocyte count for monocytes and rheumatoid arthritis for B cells (right panel). A zoomable version of this figure can be found at: https://www.easyzoom.com/imageaccess/e8c2fd02c90f456b85f629635c2f30a3

Article Snippet: We ran FORGE2 with default settings (i.e. 1000 background repetitions) and a significance threshold of q value< 0.01, across the following datasets: DNase I hotspot data from ENCODE, BLUEPRINT, and consolidated and unconsolidated Roadmap Epigenomics, 5 histone mark categories from consolidated Roadmap Epigenomics data and 15 HMM chromatin state datasets from consolidated Roadmap Epigenomics data.

Techniques:

Journal: Genome Biology

Article Title: Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

doi: 10.1186/s13059-021-02560-3

Figure Lengend Snippet: Shared and distinct tissue-specific enrichments for histone mark broadPeaks from consolidated Roadmap Epigenomics consortium data: ( A ) 231 tissue-specific enriched phenotypes from histone mark broadPeaks are shared with the set of enriched phenotypes for DNase I hotspot data for the same tissues, including examples for brain (central panel, self-reported math ability -MTAG-, H3K4me1 and H3K4me3 enrichment), heart (atrial fibrillation, H3K4me1 and H3K4me3 enrichment), kidney (estimated glomerular filtration rate or eGFR, H3K4me3 and H3K36me3 enrichment), and thymus (family history of Alzheimer’s, H3K9me3 enrichment). ( B ) 265 tissue-specific enriched phenotypes from histone mark broadPeaks are not shared with the set of enriched phenotypes for DNase I hotspot analysis for the same tissues, including examples for brain (central panel, cognitive performance H3K4me1 enrichment), heart (electrocardiographic traits, H3K4me1 enrichment), and thymus (nodular sclerosing Hodgkin lymphoma or NSHL H3K36me3 enrichment). PR interval (P wave to initiation of QRS complex interval), QT interval (Q wave to end of T wave interval), RBCs (red blood cells), WBCs (white blood cells), MTAG (multi-trait analysis of GWAS), NSHL (nodular sclerosis Hodgkin's lymphoma), Apolipoprotein E allele E4 (APOE e4). Tissue images used here are from Roadmap Epigenomics Consortium et al., 2015 [6]. A zoomable version of this figure can be found at: https://www.easyzoom.com/imageaccess/196e07438d2f48f6b24cb378d65f31b7

Article Snippet: We ran FORGE2 with default settings (i.e. 1000 background repetitions) and a significance threshold of q value< 0.01, across the following datasets: DNase I hotspot data from ENCODE, BLUEPRINT, and consolidated and unconsolidated Roadmap Epigenomics, 5 histone mark categories from consolidated Roadmap Epigenomics data and 15 HMM chromatin state datasets from consolidated Roadmap Epigenomics data.

Techniques: Filtration

Journal: Genome Biology

Article Title: Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

doi: 10.1186/s13059-021-02560-3

Figure Lengend Snippet: GWAS enrichments for enhancer (Enh) HMM chromatin state regions from consolidated Roadmap Epigenomics consortium data: ( A ) Shown are significant tissue-specific enrichment results ( q value < 0.01, BH correction) for a representative random subset with 40 phenotypes from FORGE2 analysis across the NHGRI/EBI GWAS catalogue (downloaded 2 September 2019, full set shown in Additional File : Figure S19). GWAS phenotypes (rows) are clustered using complete linkage clustering (Euclidean distance), while different tissues and cell types (columns) are grouped according to related tissue or cell type categories (e.g. white blood cell categories are placed together, as are fibroblast categories, etc.). Values are row-normalised, with reference lineplot on the left indicating top enrichment value for each category. Clustering reveals grouping of related phenotypes with similar tissue-specific enrichment profiles. We highlighted several groups from each tissue, including phenotypes such as self-reported allergy for blood cells, atrial fibrillation for heart tissue or high-density lipoprotein (HDL) cholesterol levels for liver. ( B ) Number of shared vs unique (non-shared) tissue-specific enrichment profiles for different GWAS phenotypes across 15 chromatin states. ( C ) Venn diagram showing number of shared and unique (non-shared) phenotypes between DNase-seq datasets (DNase I hotspots), chromatin states and histone mark broadPeak datasets. The largest category is unique enriched phenotypes for histone mark broadPeaks (204, 34.8%), followed by shared enriched phenotypes across all three categories (160, 27.3%). A zoomable version of this figure can be found at: https://www.easyzoom.com/imageaccess/9e3b9bab699148f586db26ad36ba0002

Article Snippet: We ran FORGE2 with default settings (i.e. 1000 background repetitions) and a significance threshold of q value< 0.01, across the following datasets: DNase I hotspot data from ENCODE, BLUEPRINT, and consolidated and unconsolidated Roadmap Epigenomics, 5 histone mark categories from consolidated Roadmap Epigenomics data and 15 HMM chromatin state datasets from consolidated Roadmap Epigenomics data.

Techniques:

Journal: Genome Biology

Article Title: Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

doi: 10.1186/s13059-021-02560-3

Figure Lengend Snippet: Relationship between enriched GWAS phenotypes for different epigenomic marks from consolidated Roadmap Epigenomics consortium data: heatmap showing the number of tissue-specific enriched phenotypes ( q value < 0.01, BH correction) for FORGE2 analysis across the GWAS catalogue for DNase I hotspots, histone mark broadPeaks and HMM chromatin states. Epigenomic mark categories are clustered using complete linkage clustering (Euclidean distance), across rows and columns. Clustering reveals 5 main groups of epigenomic marks, coloured in purple (group 1), dark blue (group 2), green (group 3), yellow (group 4), and light blue (group 5). A zoomable version of this figure can be found at: https://www.easyzoom.com/imageaccess/4e114698194f492faa1d6812d325cd30

Article Snippet: We ran FORGE2 with default settings (i.e. 1000 background repetitions) and a significance threshold of q value< 0.01, across the following datasets: DNase I hotspot data from ENCODE, BLUEPRINT, and consolidated and unconsolidated Roadmap Epigenomics, 5 histone mark categories from consolidated Roadmap Epigenomics data and 15 HMM chromatin state datasets from consolidated Roadmap Epigenomics data.

Techniques:

Journal: Genome Biology

Article Title: Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

doi: 10.1186/s13059-021-02560-3

Figure Lengend Snippet: Myeloproliferative neoplasm GWAS enrichment for DNase I hotspots and consolidated histone mark broadPeaks from Roadmap Epigenomics consortium data: ( A ) Significant tissue- and cell type-specific enrichment results ( q value < 0.01, Benjamini-Hochberg (BH) correction) for FORGE2 DNase I hotspot analysis on 25 suggestive MPN GWAS associations ( p value < 1 × 10 −6 ). Different tissues and cell types (rows) are grouped according to related tissue or cell type categories (e.g. white blood cell categories are placed together, as are fibroblast categories, etc.). FORGE2 DNase I hotspot analysis reveals a cell type-specific enrichment profile for CD34+ haematopoietic stem cells (red dot). ( B ) Significant tissue- and cell type-specific enrichment results ( q value < 0.01, Benjamini-Hochberg (BH) correction) for FORGE2 histone mark broadPeak analysis for the same variants. Different tissues and cell types (rows) are grouped according to related tissue or cell type categories (e.g. white blood cell categories are placed together, as are fibroblast categories, etc.). Here, FORGE2 analysis reveals a cell type-specific enrichment profile for CD34+ haematopoietic stem cell H3K4me1 broadPeaks, a mark enriched for enhancer regions (red dot). A zoomable version of this figure can be found at: https://www.easyzoom.com/imageaccess/3245f515d6894a8eb644b35ea22b2ef5

Article Snippet: We ran FORGE2 with default settings (i.e. 1000 background repetitions) and a significance threshold of q value< 0.01, across the following datasets: DNase I hotspot data from ENCODE, BLUEPRINT, and consolidated and unconsolidated Roadmap Epigenomics, 5 histone mark categories from consolidated Roadmap Epigenomics data and 15 HMM chromatin state datasets from consolidated Roadmap Epigenomics data.

Techniques: