ArticleHuman molecular genetics2017
Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index.International journal of epidemiology · 2022Pooled it
- Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis.Nature genetics · 2018Pooled it
- SMAD3 Gene Polymorphisms and Protein Expression as Potential Biomarkers of Susceptibility to Knee Osteoarthritis.Cureus · 2026Article
- Genome-wide association study of frailty and integrative functional analysis to elucidate its relationship with aging.GeroScience · 2026Article
- Revealing the mediating mechanisms between BMI and osteoarthritis: a Mendelian randomization and mediation analysis.Aging clinical and experimental research · 2025Article
- Genetic markers for knee osteoarthritis presence are not associated with disease progression - data from the IMI-APPROACH cohort.PloS one · 2025Article
- Osteoporosis and osteoarthritis: a bi-directional Mendelian randomization study.Arthritis research & therapy · 2023Article
- Genetics of osteoarthritis.Osteoarthritis and cartilage · 2022Review
- Prognostic value of small mother against decapentaplegic expression in human gastric cancer.Bioengineered · 2021Article
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- The Genetic Epidemiology of Joint Shape and the Development of Osteoarthritis.Calcified tissue international · 2021Review
- The Association of Lumbar Disc Herniation with Lumbar Volumetric Bone Mineral Density in a Cross-Sectional Chinese Study.Diagnostics (Basel, Switzerland) · 2021Article
- Pleiotropic associations of heterozygosity for theERJ open research · 2021Article
- Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics.Current osteoporosis reports · 2021Review
- Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.Arthritis research & therapy · 2021Article
- Defining disease progression in Chinese mainland people: Association between bone mineral density and knee osteoarthritis.Journal of orthopaedic translation · 2021Article
- Identification of key genes in osteoarthritis using bioinformatics, principal component analysis and meta-analysis.Experimental and therapeutic medicine · 2021Article
- Genetic Pleiotropy of Bone-Related Phenotypes: Insights from Osteoporosis.Current osteoporosis reports · 2020Review
- The use of technology in the subcategorisation of osteoarthritis: a Delphi study approach.Osteoarthritis and cartilage open · 2020Article
- Inhibition of microRNA-221-5p induces osteogenic differentiation by directly targeting smad3 in myeloma bone disease mesenchymal stem cells.Oncology letters · 2019Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
Abstract
Osteoarthritis (OA) is a common complex disease with high public health burden and no curative therapy. High bone mineral density (BMD) is associated with an increased risk of developing OA, suggesting a shared underlying biology. Here, we performed the first systematic overlap analysis of OA and BMD on a genome wide scale. We used summary statistics from the GEFOS consortium for lumbar spine (n = 31,800) and femoral neck (n = 32,961) BMD, and from the arcOGEN consortium for three OA phenotypes (hip, ncases=3,498; knee, ncases=3,266; hip and/or knee, ncases=7,410; ncontrols=11,009). Performing LD score regression we found a significant genetic correlation between the combined OA phenotype (hip and/or knee) and lumbar spine BMD (rg=0.18, P = 2.23 × 10-2), which may be driven by the presence of spinal osteophytes. We identified 143 variants with evidence for cross-phenotype association which we took forward for replication in independent large-scale OA datasets, and subsequent meta-analysis with arcOGEN for a total sample size of up to 23,425 cases and 236,814 controls. We found robustly replicating evidence for association with OA at rs12901071 (OR 1.08 95% CI 1.05-1.11, Pmeta=3.12 × 10-10), an intronic variant in the SMAD3 gene, which is known to play a role in bone remodeling and cartilage maintenance. We were able to confirm expression of SMAD3 in intact and degraded cartilage of the knee and hip. Our findings provide the first systematic evaluation of pleiotropy between OA and BMD, highlight genes with biological relevance to both traits, and establish a robust new OA genetic risk locus at SMAD3.
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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.