ArticleJournal of the American Society of Nephrology : JASN2018
Chromatin Conformation Links Distal Target Genes to CKD Loci.
Article in Journal of the American Society of Nephrology : JASN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Epigenetic regulation of nephrogenesis: from Waddington's landscape to adult disease.American journal of physiology. Renal physiology · 2026Review
- Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.Nature communications · 2025Article
- Decoding Kidney Pathophysiology: Omics-Driven Approaches in Precision Medicine.Journal of personalized medicine · 2024Review
- Challenges and considerations for reproducibility of STARR-seq assays.Genome research · 2023Article
- Improvement of hemolytic anemia with GBT1118 is renoprotective in transgenic sickle mice.Blood advances · 2022Article
- Exploring high-resolution chromatin interaction changes and functional enhancers of myogenic marker genes during myogenic differentiation.The Journal of biological chemistry · 2022Article
- Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Multi-Omic Approaches to Identify Genetic Factors in Metabolic Syndrome.Comprehensive Physiology · 2021Article
- 3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing.Acta pharmaceutica Sinica. B · 2021Article
- Chromatin architecture reveals cell type-specific target genes for kidney disease risk variants.BMC biology · 2021Article
- Chromatin Conformation in Development and Disease.Frontiers in cell and developmental biology · 2021Review
- Three-dimensional genome: developmental technologies and applications in precision medicine.Journal of human genetics · 2020Article
- Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State.International journal of molecular sciences · 2020Article
- Transcriptome analysis reveals microvascular endothelial cell-dependent pericyte differentiation.Scientific reports · 2019Article
- Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1.Toxins · 2019Article
- Understanding the 3D genome: Emerging impacts on human disease.Seminars in cell & developmental biology · 2019Review
- Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci.Journal of the American Society of Nephrology : JASN · 2019Article
- QTL mapping of rat blood pressure loci on RNO1 within a homologous region linked to human hypertension on HSA15.PloS one · 2019Article
- Genome-Wide Maps of Transcription Regulatory Elements and Transcription Enhancers in Development and Disease.Comprehensive Physiology · 2018Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes. To identify target genes of these DREs, we used circular chromosome conformation capture (4C) sequencing on glomerular endothelial cells and renal tubular epithelial cells. Our 4C analyses revealed interactions of CKD-associated susceptibility regions with the transcriptional start sites of 304 target genes. Overlap with multiple databases confirmed that many of these target genes are involved in kidney homeostasis. Expression quantitative trait loci analysis revealed that mRNA levels of many target genes are genotype dependent. Pathway analyses showed that target genes were enriched in processes crucial for renal function, identifying dysregulated geranylgeranyl diphosphate biosynthesis as a potential disease mechanism. Overall, our data annotated multiple genes to previously reported CKD-associated single-nucleotide polymorphisms and provided evidence for interaction between these loci and target genes. This pipeline provides a novel technique for hypothesis generation and complements classic GWAS interpretation. Future studies are required to specify the implications of our dataset and further reveal the complex roles that common variants have in complex diseases, such as CKD.
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