SynthesisPLoS genetics2012
Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus.
Synthesis in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 5 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.
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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.
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Who cites it
100 citing papers in PubMed, 5 syntheses or guidelines pooled it, 168 citations in OpenAlex.
- Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans.PLoS genetics · 2018Pooled it
- Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.BMJ (Clinical research ed.) · 2018Pooled 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
- Identification of IDUA and WNT16 Phosphorylation-Related Non-Synonymous Polymorphisms for Bone Mineral Density in Meta-Analyses of Genome-Wide Association Studies.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Pooled it
- Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Pooled 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 risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males.Journal of bone and mineral metabolism · 2016Trial
- Genetic Risk Scores Implicated in Adult Bone Fragility Associate With Pediatric Bone Density.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Trial
- Identifying rare variants in genes related to bone phenotypes in a cohort of postmenopausal women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Article
- Regulation of WNT16 in bone may involve upstream enhancers within CPED1.Scientific reports · 2025Article
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- TheInternational journal of burns and trauma · 2024Review
- Protocol for preliminary, multicenteric validation of "PoCOsteo device": A point of care tool for proteomic and genomic study of osteoporosis.Biology methods & protocols · 2024Article
- A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
- 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
- Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.Genes & diseases · 2023Review
- Examining craniofacial variation among crispant and mutant zebrafish models of human skeletal diseases.Journal of anatomy · 2023Article
- Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 6 countries.
Funding
Abstract
To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ± 500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD) with rs917727) in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P = 2.6 × 10(-31) and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P = 1.42 × 10(-10)) for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P = 1.9 × 10(-16)) and rs7801723 (P = 8.9 × 10(-28)), also mapping to C7orf58 (r(2) = 0.50 with rs4609139). Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of osteoporosis later in life.
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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.