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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323023 | PMC |
| http://dx.doi.org/10.1016/j.ajhg.2021.05.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genome-wide analysis in northern Chinese twins identifies twelve new susceptibility loci for pulmonary function.
BMC Genomics
December 2024
Department of Epidemiology and Health Statistics, The College of Public Health, Qingdao University, NO. 308 Ning Xia Street, Qingdao, Shandong Province, 266071, People's Republic of China.
Background: Previous genome-wide association studies (GWAS) have established association between genetic variants and pulmonary function across various ethnics, whereas such associations are scarcely reported in Chinese adults. Therefore, we conducted an GWAS to explore relationships between genetic variants and pulmonary function among middle-aged Chinese dizygotic twins and further validated the top variants using data from the UK Biobank (UKB).
Methods: In the discovery phase, 139 dizygotic twin pairs were drawn from the Qingdao Twin Registry.
GWAS-Significant Loci and Uterine Fibroids Risk: Analysis of Associations, Gene-Gene and Gene-Environmental Interactions.
Front Biosci (Schol Ed)
December 2024
Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.
Background: Uterine fibroids (UF) is the most common benign tumour of the female reproductive system. We investigated the joint contribution of genome-wide association studies (GWAS)-significant loci and environment-associated risk factors to the UF risk, along with epistatic interactions between single nucleotide polymorphisms (SNPs).
Methods: DNA samples from 737 hospitalised patients with UF and 451 controls were genotyped using probe-based PCR for seven common GWAS SNPs: rs117245733 , rs547025 rs2456181 , rs7907606 , , rs58415480 , rs7986407 , and rs72709458 .
Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality.
Front Nutr
December 2024
The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.
Background: This study delves into the complex interplay between genetics, 25-hydroxyvitamin D (25OHD), and schizophrenia (SCZ). It leverages extensive sample data derived from Genome-Wide Association Studies (GWAS) to uncover genetic correlations.
Methods: Employing Linkage Disequilibrium Score Regression (LDSC) and S-LDSC, this study investigates genetic connections between 25OHD and SCZ.
Genome-wide association study on chronic postsurgical pain after abdominal surgeries in the UK Biobank.
Anaesthesia
December 2024
Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands.
Introduction: Chronic pain is one of the most common and severe complications after surgery, affecting quality of life and overall wellbeing of patients. Several risk factors have been identified but the mechanisms of chronic postsurgical pain development remain unclear. This study aimed to identify single-nucleotide polymorphisms associated with developing chronic postsurgical pain after abdominal surgery, one of the most common types of surgery.
View Article and Find Full Text PDFBackground: Considering that the treatment of gout is poor, we performed a Mendelian randomization (MR) study to identify candidate biomarkers and therapeutic targets for gout.
Methods: A drug-targeted MR study was performed for gout by integrating the gout genome-wide association studies (GWAS) summary data and cis expression quantitative trait loci of 2,633 druggable genes from multiple cohorts. Summary data-based Mendelian randomization (SMR) analyses based on transcript and protein levels were further implemented to validate the reliability of the identified potential therapeutic targets for gout.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!