ArticleAmerican journal of human genetics2021
Topologically associating domain boundaries that are stable across diverse cell types are evolutionarily constrained and enriched for heritability.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 205 citations in OpenAlex.
- DeCTCF: Decoding CTCF binding sequences by leveraging predicted epigenomic features.PLoS computational biology · 2026Article
- Foundation model reveals the shared organization of transcription and topologically associating domains.Cell systems · 2026Article
- The dark genome in cardiovascular medicine.European heart journal · 2026Review
- Systematic evaluation of the heterogeneity of topologically associating domain boundaries in a large genomic context in humans.NAR genomics and bioinformatics · 2026Article
- Bridging precision agriculture and human medicine through comparative genetics.Nature reviews. Genetics · 2026Review
- Genomic Evidence for Natural Selection Underlying High-Altitude Adaptive Hemoglobin Levels Among Peruvian Andeans.Genome biology and evolution · 2026Article
- Evolution of CTCF binding sites in the human genome.Molecular biology and evolution · 2026Article
- Review
- A TAD-informed aging-brain xQTL atlas of multi-modal and cell-type-resolved regulatory variation.medRxiv : the preprint server for health sciences · 2026Article
- A Multi-Context Regulome-Wide Association Atlas for Genetic Studies of Aging Brain Disorders.medRxiv : the preprint server for health sciences · 2026Article
- Dynamic reorganization of three-dimensional genome architecture during Populus diversification.Nature ecology & evolution · 2026Article
- Ryder: Epigenome normalization using a two-tier model and internal reference regions.bioRxiv : the preprint server for biology · 2026Article
- GWAS SVatalog: a visualization tool to aid fine-mapping of GWAS loci with structural variations.Heredity · 2026Article
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
- X-linked severe combined immunodeficiency due toFrontiers in immunology · 2026Article
- Distributional genetic effects reveal context-dependent molecular regulation in human brain aging and Alzheimer's disease.Research square · 2025Article
- Chromosome compartment assembly is essential for subtelomeric gene silencing in trypanosomes.Nature communications · 2025Article
- Interaction Between Enhancers and Promoters in Chicken Genome.International journal of molecular sciences · 2025Article
- Structural variants in the 3D genome as drivers of disease.Nature reviews. Genetics · 2025Review
- Reconstructing the 3D genome organization of Neanderthals reveals that chromatin folding shaped phenotypic and sequence divergence.bioRxiv : the preprint server for biology · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Topologically associating domains (TADs) are fundamental units of three-dimensional (3D) nuclear organization. The regions bordering TADs-TAD boundaries-contribute to the regulation of gene expression by restricting interactions of cis-regulatory sequences to their target genes. TAD and TAD-boundary disruption have been implicated in rare-disease pathogenesis; however, we have a limited framework for integrating TADs and their variation across cell types into the interpretation of common-trait-associated variants. Here, we investigate an attribute of 3D genome architecture-the stability of TAD boundaries across cell types-and demonstrate its relevance to understanding how genetic variation in TADs contributes to complex disease. By synthesizing TAD maps across 37 diverse cell types with 41 genome-wide association studies (GWASs), we investigate the differences in disease association and evolutionary pressure on variation in TADs versus TAD boundaries. We demonstrate that genetic variation in TAD boundaries contributes more to complex-trait heritability, especially for immunologic, hematologic, and metabolic traits. We also show that TAD boundaries are more evolutionarily constrained than TADs. Next, stratifying boundaries by their stability across cell types, we find substantial variation. Compared to boundaries unique to a specific cell type, boundaries stable across cell types are further enriched for complex-trait heritability, evolutionary constraint, CTCF binding, and housekeeping genes. Thus, considering TAD boundary stability across cell types provides valuable context for understanding the genome's functional landscape and enabling variant interpretation that takes 3D structure into account.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.