ArticleNature genetics2017
Ancient selection for derived alleles at a GDF5 enhancer influencing human growth and osteoarthritis risk.
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 4 of them syntheses 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
62 citing papers in PubMed, 4 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Genetics of hip dysplasia - a systematic literature review.BMC musculoskeletal disorders · 2024Pooled it
- Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.Nature communications · 2021Pooled it
- Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: a meta-analysis.Arthritis research & therapy · 2020Pooled it
- Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nature genetics · 2018Pooled it
- TheGenes · 2025Observational
- 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
- Genetic Architecture of Immune Cell DNA Methylation in the Rhesus Macaque.Molecular ecology · 2025Article
- How aging causes osteoarthritis: An evolutionary physiology perspective.Osteoarthritis and cartilage · 2025Review
- An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis.Cell genomics · 2025Article
- Article
- Functional genomics of human skeletal development and the patterning of height heritability.Cell · 2025Article
- The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk.American journal of human genetics · 2024Article
- A conserved transcription factor regulatory program promotes tendon fate.Developmental cell · 2024Article
- Contemporary small-scale subsistence populations offer unique insights into human musculoskeletal health and aging.Science advances · 2024Review
- Article
- Parallel Evolution at the Regulatory Base-Pair Level Contributes to Mammalian Interspecific Differences in Polygenic Traits.Molecular biology and evolution · 2024Article
- Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development.Nature communications · 2024Article
- GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications.Journal of hepatocellular carcinoma · 2024Review
- Genetic risk of osteoarthritis operates during human skeletogenesis.Human molecular genetics · 2023Article
2 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
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Variants in GDF5 are associated with human arthritis and decreased height, but the causal mutations are still unknown. We surveyed the Gdf5 locus for regulatory regions in transgenic mice and fine-mapped separate enhancers controlling expression in joints versus growing ends of long bones. A large downstream regulatory region contains a novel growth enhancer (GROW1), which is required for normal Gdf5 expression at ends of developing bones and for normal bone lengths in vivo. Human GROW1 contains a common base-pair change that decreases enhancer activity and colocalizes with peaks of positive selection in humans. The derived allele is rare in Africa but common in Eurasia and is found in Neandertals and Denisovans. Our results suggest that an ancient regulatory variant in GROW1 has been repeatedly selected in northern environments and that past selection on growth phenotypes explains the high frequency of a GDF5 haplotype that also increases arthritis susceptibility in many human populations.
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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.