SynthesisPLoS genetics2013
Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.
Synthesis in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
64 citing papers in PubMed, 5 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Pooled it
- Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.Communications biology · 2023Pooled it
- Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.American journal of human genetics · 2018Pooled it
- Association of 3q13.32 variants with hip trochanter and intertrochanter bone mineral density identified by a genome-wide association study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Pooled it
- Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.Human molecular genetics · 2014Pooled 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
- Bone Health and Physical Activity - The Complex Mechanism.Aging and disease · 2024Review
- Trabecular architecture of the distal femur in extant hominids.Journal of anatomy · 2024Article
- GREM2 inactivation increases trabecular bone mass in mice.Scientific reports · 2024Article
- Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know.Current osteoporosis reports · 2024Review
- Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program.PloS one · 2024Article
- Article
- Genetic Association of rs1021188 and DNA Methylation Signatures ofFrontiers in medicine · 2022Article
- The genetic overlap between osteoporosis and craniosynostosis.Frontiers in endocrinology · 2022Review
- A transcriptome-wide association study to detect novel genes for volumetric bone mineral density.Bone · 2021Article
- The Polygenic and Monogenic Basis of Paediatric Fractures.Current osteoporosis reports · 2021Review
- RSPO3 is important for trabecular bone and fracture risk in mice and humans.Nature communications · 2021Article
- Cortical and trabecular bone structure of the hominoid capitate.Journal of anatomy · 2021Article
- Article
- 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
4 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
21 authors at 10 institutions in 4 countries.
Funding
Abstract
Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10⁻¹⁴; LOC285735, rs271170, p = 2.7×10⁻¹²; OPG, rs7839059, p = 1.2×10⁻¹⁰; and ESR1/C6orf97, rs6909279, p = 1.1×10⁻⁹). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10⁻⁹). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.
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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 Socratic graph.