ArticleHuman molecular genetics2023
Genetic risk of osteoarthritis operates during human skeletogenesis.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- HK1-LDHA axis feedback regulation promotes histone lactylation of Wnt5a and mediates prenatal acetaminophen-induced susceptibility to osteoarthritis in male offspring.Experimental & molecular medicine · 2026Article
- Dissecting the genetic architecture of knee alignment reveals its contribution to osteoarthritis risk.medRxiv : the preprint server for health sciences · 2026Article
- Human hip osteoarthritis-associatedbioRxiv : the preprint server for biology · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.American journal of human genetics · 2026Article
- Gene Polymorphisms Associated with Osteoarthritis: Potential Implications for Nutrigenetics and Precision Nutrition.Nutrients · 2026Review
- Programmed cell death in osteoarthritis.Apoptosis : an international journal on programmed cell death · 2026Review
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.bioRxiv : the preprint server for biology · 2025Article
- Complex Regulatory Interactions at GDF5 Shape Joint Morphology and Osteoarthritis Disease Risk.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Review
- From mechanism to medicine: The progress and potential of epigenetics in osteoarthritis.Osteoarthritis and cartilage open · 2025Review
- Extrachromosomal circular DNAs in the differentiation of human bone marrow mesenchymal stem cells.Stem cell research & therapy · 2025Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.Cell genomics · 2025Article
- Therapeutic Controlled Release Strategies for Human Osteoarthritis.Advanced healthcare materials · 2025Review
- Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis.American journal of human genetics · 2024Article
- The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk.American journal of human genetics · 2024Article
- Article
- Osteoarthritis as an Enhanceropathy: Gene Regulation in Complex Musculoskeletal Disease.Current rheumatology reports · 2024Review
- Specific isoforms of the ubiquitin ligase gene WWP2 are targets of osteoarthritis genetic risk via a differentially methylated DNA sequence.Arthritis research & therapy · 2024Article
- 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
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Osteoarthritis (OA) is a polygenic disease of older people resulting in the breakdown of cartilage within articular joints. Although it is a leading cause of disability, there are no disease-modifying therapies. Evidence is emerging to support the origins of OA in skeletogenesis. Whereas methylation quantitative trait loci (mQTLs) co-localizing with OA genome-wide association study signals have been identified in aged human cartilage and used to identify effector genes and variants, such analyses have never been conducted during human development. Here, for the first time, we have investigated the developmental origins of OA genetic risk at seven well-characterized OA risk loci, comprising 39 OA-mQTL CpGs, in human fetal limb (FL) and cartilage (FC) tissues using a range of molecular genetic techniques. We identified significant OA-mQTLs at 14 and 29 CpGs in FL and FC tissues, respectively, and compared our results with aged cartilage samples (AC). Differential methylation was observed at 26 sites between FC and AC, with the majority becoming actively hypermethylated in old age. Notably, 6/9 OA effector genes showed allelic expression imbalances during fetal development. Finally, we conducted ATAC-sequencing in cartilage from the developing and aged hip and knee to identify accessible chromatin regions and found enrichment for transcription factor binding motifs including SOX9 and FOS/JUN. For the first time, we have demonstrated the activity of OA-mQTLs and expression imbalance of OA effector genes during human skeletogenesis. We show striking differences in the spatiotemporal function of these loci, contributing to our understanding of OA aetiology, with implications for the timing and strategy of pharmacological interventions.
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