SynthesisAnnals of internal medicine2009
Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture.
Synthesis in Annals of internal medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 11 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
120 citing papers in PubMed, 11 syntheses or guidelines pooled it, 278 citations in OpenAlex.
- Combined effects of physical activity and calcium on bone health in children and adolescents: a systematic review of randomized controlled trials.World journal of pediatrics : WJP · 2020Pooled it
- Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.BMC genomics · 2016Pooled it
- Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.Annals of the rheumatic diseases · 2013Pooled it
- Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis.Molecular biology reports · 2013Pooled it
- Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.Annals of the rheumatic diseases · 2013Pooled it
- Association of MTHFR C667T polymorphism with bone mineral density and fracture risk: an updated meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2012Pooled it
- WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.PLoS genetics · 2012Pooled it
- Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.Nature genetics · 2012Pooled it
- Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2011Pooled it
- Polymorphisms in the 5' flank of COL1A1 gene and osteoporosis: meta-analysis of published studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2011Pooled it
- Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.PLoS genetics · 2010Pooled it
- Association of a polygenic risk score with low trauma fractures in people with HIV - The swiss HIV cohort study.PloS one · 2026Article
- The Influence of Clinical Factors and Genetic Variants ofInternational journal of molecular sciences · 2025Article
- Influence of ATG SNPs on hip fracture patients' functional status.Scientific reports · 2025Observational
- Multi-omics insights into bone tissue injury and healing: bridging orthopedic trauma and regenerative medicine.Burns & trauma · 2025Review
- SNPs in GPCR Genes and Impaired Osteogenic Potency in Osteoporotic Patient Lines-Based Study.International journal of molecular sciences · 2024Article
- Between a Rock and a Short Place-The Impact of Nephrolithiasis on Skeletal Growth and Development Across the Lifespan.Current osteoporosis reports · 2024Review
- Article
- Polymorphism of LRP4 Gene (rs9667108) among Post Menopause Women with Osteoporosis.Iranian journal of public health · 2023Article
- Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
35 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundOsteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies.
objectiveTo assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes.
designLarge-scale meta-analysis of genome-wide association data.
setting5 international, multicenter, population-based studies.
participantsData on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands. MEASUREMENTS: Systematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures.
results150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST. LIMITATION: Only common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded.
conclusionIn this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.
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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.