SynthesisPLoS genetics2010
Genome-wide association meta-analysis of cortical bone mineral density unravels allelic heterogeneity at the RANKL locus and potential pleiotropic effects on bone.
Synthesis in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- P4 medicine and osteoporosis: a systematic review.Wiener klinische Wochenschrift · 2016Pooled it
- Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.PLoS genetics · 2013Pooled it
- WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.PLoS genetics · 2012Pooled it
- Multidimensional Bone Density Phenotyping Reveals New Insights Into Genetic Regulation of the Pediatric Skeleton.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Trial
- Genetic and Gene Expression Resources for Osteoporosis and Bone Biology Research.Current osteoporosis reports · 2023Review
- A study of the influence of genetic variance and sex on the density and thickness of the calvarial bone in collaborative cross mice.Animal models and experimental medicine · 2023Article
- Genetic Association of rs1021188 and DNA Methylation Signatures ofFrontiers in medicine · 2022Article
- The genetic overlap between osteoporosis and craniosynostosis.Frontiers in endocrinology · 2022Review
- Longer or shorter spines: Reciprocal trait evolution in stickleback via triallelic regulatory changes inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications.Bone research · 2021Review
- Factors influencing peak bone mass gain.Frontiers of medicine · 2021Review
- Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques.Frontiers in endocrinology · 2021Review
- Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").Frontiers in endocrinology · 2021Review
- BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure.The Journal of clinical endocrinology and metabolism · 2020Article
- A genome-wide association study in mice reveals a role for Rhbdf2 in skeletal homeostasis.Scientific reports · 2020Article
- Opportunities and Challenges in Functional Genomics Research in Osteoporosis: Report From a Workshop Held by the Causes Working Group of the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society on October 5th 2020.Frontiers in endocrinology · 2020Review
- Association of Genetic Variants ofMediators of inflammation · 2019Article
- Article
- Mechanical basis of bone strength: influence of bone material, bone structure and muscle action.Journal of musculoskeletal & neuronal interactions · 2017Review
- Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population.International journal of medical sciences · 2017Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Previous genome-wide association (GWA) studies have identified SNPs associated with areal bone mineral density (aBMD). However, this measure is influenced by several different skeletal parameters, such as periosteal expansion, cortical bone mineral density (BMD(C)) cortical thickness, trabecular number, and trabecular thickness, which may be under distinct biological and genetic control. We have carried out a GWA and replication study of BMD(C), as measured by peripheral quantitative computed tomography (pQCT), a more homogenous and valid measure of actual volumetric bone density. After initial GWA meta-analysis of two cohorts (ALSPAC n = 999, aged ∼15 years and GOOD n = 935, aged ∼19 years), we attempted to replicate the BMD(C) associations that had p<1×10(-5) in an independent sample of ALSPAC children (n = 2803) and in a cohort of elderly men (MrOS Sweden, n = 1052). The rs1021188 SNP (near RANKL) was associated with BMD(C) in all cohorts (overall p = 2×10(-14), n = 5739). Each minor allele was associated with a decrease in BMD(C) of ∼0.14SD. There was also evidence for an interaction between this variant and sex (p = 0.01), with a stronger effect in males than females (at age 15, males -6.77mg/cm(3) per C allele, p = 2×10(-6); females -2.79 mg/cm(3) per C allele, p = 0.004). Furthermore, in a preliminary analysis, the rs1021188 minor C allele was associated with higher circulating levels of sRANKL (p<0.005). We show this variant to be independent from the previously aBMD associated SNP (rs9594738) and possibly from a third variant in the same RANKL region, which demonstrates important allelic heterogeneity at this locus. Associations with skeletal parameters reflecting bone dimensions were either not found or were much less pronounced. This finding implicates RANKL as a locus containing variation associated with volumetric bone density and provides further insight into the mechanism by which the RANK/RANKL/OPG pathway may be involved in skeletal development.
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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.