ArticleNature communications2021
Joint disease-specificity at the regulatory base-pair level.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Developmental Dysplasia of the Hip in Saudi Arabia and the Gulf Countries:Saudi medical journal · 2026Pooled it
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- In Vitro Massively Parallel Screening of Human Regulatory Elements Involved in Postcranial Skeletal Development for Differential Activity Compared to Chimpanzee.Genome biology and evolution · 2026Article
- Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026Review
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- The roles of TGF-β, Wnt, and MAPK signaling pathways in joint lineage specification in vitro and ex vivo.Stem cell reports · 2025Article
- Complex Regulatory Interactions at GDF5 Shape Joint Morphology and Osteoarthritis Disease Risk.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- From mechanism to medicine: The progress and potential of epigenetics in osteoarthritis.Osteoarthritis and cartilage open · 2025Review
- Fgfr3 enhancer deletion markedly improves all skeletal features in a mouse model of achondroplasia.The Journal of clinical investigation · 2025Article
- Functional genomics of human skeletal development and the patterning of height heritability.Cell · 2025Article
- Parallel Evolution at the Regulatory Base-Pair Level Contributes to Mammalian Interspecific Differences in Polygenic Traits.Molecular biology and evolution · 2024Article
- Molecular mechanisms and genetic factors contributing to the developmental dysplasia of the hip.Frontiers in genetics · 2024Review
- HOXA10 promotes Gdf5 expression in articular chondrocytes.Scientific reports · 2023Article
- Human-specific genetics: new tools to explore the molecular and cellular basis of human evolution.Nature reviews. Genetics · 2023Review
- Genetic risk of osteoarthritis operates during human skeletogenesis.Human molecular genetics · 2023Article
- Mediation of the Same Epigenetic and Transcriptional Effect by Independent Osteoarthritis Risk-Conferring Alleles on a Shared Target Gene, COLGALT2.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Epigenetics as a mediator of genetic risk in osteoarthritis: role during development, homeostasis, aging, and disease progression.American journal of physiology. Cell physiology · 2023Review
- Sox, Fox, and Lmx1b binding sites differentially regulate a Gdf5-Associated regulatory region during elbow development.Frontiers in cell and developmental biology · 2023Article
- 3D chromatin structure in chondrocytes identifies putative osteoarthritis risk genes.Genetics · 2022Article
- The developmental impacts of natural selection on human pelvic morphology.Science advances · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Given the pleiotropic nature of coding sequences and that many loci exhibit multiple disease associations, it is within non-coding sequence that disease-specificity likely exists. Here, we focus on joint disorders, finding among replicated loci, that GDF5 exhibits over twenty distinct associations, and we identify causal variants for two of its strongest associations, hip dysplasia and knee osteoarthritis. By mapping regulatory regions in joint chondrocytes, we pinpoint two variants (rs4911178; rs6060369), on the same risk haplotype, which reside in anatomical site-specific enhancers. We show that both variants have clinical relevance, impacting disease by altering morphology. By modeling each variant in humanized mice, we observe joint-specific response, correlating with GDF5 expression. Thus, we uncouple separate regulatory variants on a common risk haplotype that cause joint-specific disease. By broadening our perspective, we finally find that patterns of modularity at GDF5 are also found at over three-quarters of loci with multiple GWAS disease associations.
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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.