Similar Datasets
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTLs) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTLs have been identified in a limited set of human tissues. Here we mapped caQTLs in human liver tissue in 20 liver samples and identified 3,123 caQTLs. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTLs. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTLs and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTLs contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
| S-EPMC8323023 | biostudies-literature
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164938 | GEO
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164876 | GEO
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164870 | GEO
Project description:Genetic effects on liver chromatin accessibility identify disease regulatory variants
| PRJNA692488 | ENA
Project description:Genetic effects on liver chromatin accessibility identify disease regulatory variants [genotypes]
| PRJNA692489 | ENA
Project description:Genetic effects on liver chromatin accessibility identify disease regulatory variants [ATAC-seq]
| PRJNA692238 | ENA
Project description:Genetic effects on liver chromatin accessibility identify disease regulatory variants [RNA-seq]
| PRJNA692245 | ENA
Project description:Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.
| S-EPMC9623183 | biostudies-literature
Project description:The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the generegulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.
| S-EPMC9095509 | biostudies-literature