التفاصيل البيبلوغرافية
| العنوان: |
Chromatin Landscapes of Human Lung Cells Predict Potentially Functional Chronic Obstructive Pulmonary Disease Genome-Wide Association Study Variants. |
| المؤلفون: |
Benway, Christopher J., Jiangyuan Liu, Feng Guo, Fei Du, Randell, Scott H., Cho, Michael H., Silverman, Edwin K., Xiaobo Zhou |
| المصدر: |
American Journal of Respiratory Cell & Molecular Biology; Jul2021, Vol. 65 Issue 1, p92-102, 11p |
| مصطلحات موضوعية: |
GENOME-wide association studies, MOLECULAR epidemiology, OBSTRUCTIVE lung diseases, LUNG diseases, CHROMATIN |
| مستخلص: |
Genome-wide association studies (GWASs) have identified dozens of loci associated with risk of chronic obstructive pulmonary disease (COPD). However, identifying the causal variants and their functional role in the appropriate cell type remains a major challenge. We aimed to identify putative causal variants in 82 GWAS loci associated with COPD susceptibility and predict the regulatory impact of these variants in lung-cell types. We used an integrated approach featuring statistical fine mapping, open chromatin profiling, and machine learning to identify functional variants. We generated chromatin accessibility data using the Assay for Transposase-Accessible Chromatin with High-Throughput Sequencing (ATAC-seq) for human primary lung-cell types implicated in COPD pathobiology. We then evaluated the enrichment of COPD risk variants in lung-specific open chromatin regions and generated cell type-specific regulatory predictions for .6,500 variants corresponding to 82 COPD GWAS loci. Integration of the fine-mapped variants with lung open chromatin regions helped prioritize 22 variants in putative regulatory elements with potential functional effects. Comparison with functional predictions from 222 Encyclopedia of DNA Elements (ENCODE) cell samples revealed cell type-specific regulatory effects of COPD variants in the lung epithelium, endothelium, and immune cells. We identified potential causal variants for COPD risk by integrating fine mapping in GWAS loci with cell-specific regulatory profiling, highlighting the importance of leveraging the chromatin status in relevant cell types to predict the molecular effects of risk variants in lung disease. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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