SynthesisBMC genomics2016
Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.
Synthesis in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Metaanalysis Reveals Genetic Correlates of Osteoporosis Pathogenesis.The Journal of rheumatology · 2021Pooled it
- Multitrait genome association analysis identifies new susceptibility genes for human anthropometric variation in the GCAT cohort.Journal of medical genetics · 2018Pooled it
- Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs.Scientific reports · 2018Pooled it
- Comprehensive Analysis of the Roles of the CCDC Protein Family Play in a Range of 58 Disease Processes.Applied biochemistry and biotechnology · 2026Review
- Genome-wide Association Studies of over 30,000 Samples with Bone Mineral Density at Multiple Skeletal Sites and Its Clinical Relevance.Genomics, proteomics & bioinformatics · 2025Article
- Peak Bone Mass Formation: Modern View of the Problem.Biomedicines · 2023Review
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Identification of the genetic basis of sow pelvic organ prolapse.Frontiers in genetics · 2023Article
- The relationship between central obesity and bone mineral density: a Mendelian randomization study.Diabetology & metabolic syndrome · 2022Article
- Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Relationship between rs7586085, GALNT3 and CCDC170 gene polymorphisms and the risk of osteoporosis among the Chinese Han population.Scientific reports · 2022Article
- Review
- Article
- Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications.Bone research · 2021Review
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- Article
- Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts.Genome biology · 2020Article
- WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders.Frontiers in endocrinology · 2020Review
- Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density.Frontiers in genetics · 2020Article
- Next Generation Sequencing and Bioinformatics Analysis of Family Genetic Inheritance.Frontiers in genetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundOsteoporosis is a common and debilitating bone disease that is characterised by a low bone mineral density (BMD), a highly heritable trait. Genome-wide association studies (GWAS) have proven to be very successful in identifying common genetic variants associated with BMD adjusted for age, gender and weight, however a large portion of the genetic variance for this trait remains unexplained. There is evidence to suggest significant genetic correlation between body size traits and BMD. It has also recently been suggested that unintended bias can be introduced as a result of adjusting a phenotype for a correlated trait. We performed a GWAS meta-analysis in two populations (total n = 6,696) using BMD data adjusted for only age and gender, in an attempt to identify genetic variants associated with BMD including those that may have potential pleiotropic effects on BMD and body size traits.
resultsWe observed a single variant, rs2566752, associated with spine BMD at the genome-wide significance level in the meta-analysis (P = 3.36 × 10(-09)). Logistic regression analysis also revealed an association between rs2566752 and fracture rate in one of our study cohorts (P = 0.017, n = 5,654). This is an intronic variant located in the wntless Wnt ligand secretion mediator (WLS) gene (1p31.3), a known BMD locus which encodes an integral component of the Wnt ligand secretion pathway. Bioinformatics analyses of variants in moderate LD with rs2566752 produced strong evidence for a regulatory role for the variants rs72670452, rs17130567 and rs1430738. Expression quantitative trait locus (eQTL) analysis suggested that the variants rs12568456 and rs17130567 are associated with expression of the WLS gene in whole blood, cerebellum and temporal cortex brain tissue (P = 0.034-1.19 × 10(-23)). Gene-wide association testing using the VErsatile Gene-based Association Study 2 (VEGAS2) software revealed associations between the coiled-coil domain containing 170 (CCDC170) gene, located adjacent to the oestrogen receptor 1 (ESR1) gene, and BMD at the spine, femoral neck and total hip sites (P = 1.0 × 10(-06), 2.0 × 10(-06) and 2.0 × 10(-06) respectively).
conclusionsGenetic variation at the WLS and CCDC170/ESR1 loci were found to be significantly associated with BMD adjusted for only age and gender at the genome-wide level in this meta-analysis.
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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.