ArticlePLoS genetics2019
Mouse genome-wide association and systems genetics identifies Lhfp as a regulator of bone mass.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Genome-Wide Association Study of Reproductive Traits in Large White Pigs.Animals : an open access journal from MDPI · 2024Article
- Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment.Journal of ginseng research · 2024Article
- The role of vesicle trafficking genes in osteoblast differentiation and function.Scientific reports · 2023Article
- High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Article
- ELMO1 signaling is a promoter of osteoclast function and bone loss.Nature communications · 2021Article
- Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats.International journal of molecular medicine · 2021Article
- Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength.Nature communications · 2021Article
- Mouse Genetic Reference Populations: Cellular Platforms for Integrative Systems Genetics.Trends in genetics : TIG · 2021Review
- Article
- Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass.PLoS genetics · 2020Article
- Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna.Bone reports · 2020Article
- Mouse Systems Genetics as a Prelude to Precision Medicine.Trends in genetics : TIG · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bone mineral density (BMD) is a strong predictor of osteoporotic fracture. It is also one of the most heritable disease-associated quantitative traits. As a result, there has been considerable effort focused on dissecting its genetic basis. Here, we performed a genome-wide association study (GWAS) in a panel of inbred strains to identify associations influencing BMD. This analysis identified a significant (P = 3.1 x 10-12) BMD locus on Chromosome 3@52.5 Mbp that replicated in two separate inbred strain panels and overlapped a BMD quantitative trait locus (QTL) previously identified in a F2 intercross. The association mapped to a 300 Kbp region containing four genes; Gm2447, Gm20750, Cog6, and Lhfp. Further analysis found that Lipoma HMGIC Fusion Partner (Lhfp) was highly expressed in bone and osteoblasts. Furthermore, its expression was regulated by a local expression QTL (eQTL), which overlapped the BMD association. A co-expression network analysis revealed that Lhfp was strongly connected to genes involved in osteoblast differentiation. To directly evaluate its role in bone, Lhfp deficient mice (Lhfp-/-) were created using CRISPR/Cas9. Consistent with genetic and network predictions, bone marrow stromal cells (BMSCs) from Lhfp-/- mice displayed increased osteogenic differentiation. Lhfp-/- mice also had elevated BMD due to increased cortical bone mass. Lastly, we identified SNPs in human LHFP that were associated (P = 1.2 x 10-5) with heel BMD. In conclusion, we used GWAS and systems genetics to identify Lhfp as a regulator of osteoblast activity and bone mass.
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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.