ArticleBMC genomics2015
Collaborative cross mice in a genetic association study reveal new candidate genes for bone microarchitecture.
Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Unravelling novel and pleiotropic genes for cannon bone circumference and bone mineral density in Yorkshire pigs.Journal of animal science · 2024Pooled it
- Interindividual Genetic Differences Drive Discordance Between Serum Calcidiol and Calcitriol Concentrations in Females.Endocrinology · 2025Article
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- Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease.Molecules (Basel, Switzerland) · 2024Article
- Mechanically strained osteocyte-derived exosomes contained miR-3110-5p and miR-3058-3p and promoted osteoblastic differentiation.Biomedical engineering online · 2024Article
- Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity.JBMR plus · 2024Article
- Skeletal dysmorphology and mineralization defects in Fgf20 KO mice.Frontiers in endocrinology · 2024Article
- Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.Arthritis research & therapy · 2023Article
- Comprehensive Deciphering the Complexity of the Deep Bite: Insight from Animal Model to Human Subjects.Journal of personalized medicine · 2023Article
- Narrating the Genetic Landscape of Human Class I Occlusion: A Perspective-Infused Review.Journal of personalized medicine · 2023Article
- Skeletal Class II Malocclusion: From Clinical Treatment Strategies to the Roadmap in Identifying the Genetic Bases of Development in Humans with the Support of the Collaborative Cross Mouse Population.Journal of clinical medicine · 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
- Lowering fasting blood glucose with non-dialyzable material of cranberry extract is dependent on host genetic background, sex and diet.Animal models and experimental medicine · 2023Article
- Genome-wide detection of genetic structure and runs of homozygosity analysis in Anhui indigenous and Western commercial pig breeds using PorcineSNP80k data.BMC genomics · 2022Article
- Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway.Pharmaceutical biology · 2021Article
- Studying host genetic background effects on multimorbidity of intestinal cancer development, type 2 diabetes and obesity in response to oral bacterial infection and high-fat diet using the collaborative cross (CC) lines.Animal models and experimental medicine · 2021Article
- Characterization of genetically complex Collaborative Cross mouse strains that model divergent locomotor activating and reinforcing properties of cocaine.Psychopharmacology · 2020Article
- Article
- A genome-wide association study in mice reveals a role for Rhbdf2 in skeletal homeostasis.Scientific reports · 2020Article
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4 authors.
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Abstract
backgroundThe microstructure of trabecular bone is a composite trait governed by a complex interaction of multiple genetic determinants. Identifying these genetic factors should significantly improve our ability to predict of osteoporosis and its associated risks. Genetic mapping using collaborative cross mice (CC), a genetically diverse recombinant inbred mouse reference panel, offers a powerful tool to identify causal loci at a resolution under one mega base-pairs, with a relatively small cohort size. Here, we utilized 31 CC lines (160 mice of both sexes in total) to perform genome-wide haplotype mapping across 77,808 single-nucleotide polymorphisms (SNPs). Haplotype scans were refined by imputation with the catalogue of sequence variation segregating in the CC to suggest potential candidate genes. Trabecular traits were obtained following microtomographic analysis, performed on 10-μm resolution scans of the femoral distal metaphysis. We measured the trabecular bone volume fraction (BV/TV), number (Tb.N), thickness (Tb.Th), and connectivity density (Conn.D).
resultsHeritability of these traits ranged from 0.6 to 0.7. In addition there was a significant (P < 0.01) sex effect in all traits except Tb.Th. Our haplotype scans yielded six quantitative trait loci (QTL) at 1 % false discovery rate; BV/TV and Tb.Th produced two proximal loci each, on chromosome 2 and 7, respectively, and Tb.N and Conn.D yielded one locus on chromosomes 8 and 14, respectively. We identified candidate genes with previously-reported functions in bone biology, and implicated unexpected genes whose function in bone biology has yet to be assigned. Based on the literature, among the genes that ranked particularly high in our analyses (P < 10(-6)) and which have a validated causal role in skeletal biology, are Avp, Oxt, B2m (associated with BV/TV), Cnot7 (with Tb.N), Pcsk6, Rgma (with Tb.Th), Rb1, and Cpb2 (with Conn.D). Other candidate genes strongly suggested by our analyses are Sgcz, Fgf20 (associated with Tb.N), and Chd2 (with Tb.Th).
conclusionWe have demonstrated for the first time genome-wide significant association between several genetic loci and trabecular microstructural parameters for genes with previously reported experimental observations, as well as proposing a role for new candidate genes with no previously characterized skeletal function.
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