ArticleHuman molecular genetics2015
Targeted sequencing of the Paget's disease associated 14q32 locus identifies several missense coding variants in RIN3 that predispose to Paget's disease of bone.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Pooled it
- Article
- The Paget's disease of bone risk gene PML is a negative regulator of osteoclast differentiation and bone resorption.Disease models & mechanisms · 2022Article
- Attenuated clinical and osteoclastic phenotypes of Paget's disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene.BMC medical genomics · 2022Article
- Update on the pathogenesis and genetics of Paget's disease of bone.Frontiers in cell and developmental biology · 2022Review
- Epigenetic DNA Methylation Signatures Associated With the Severity of Paget's Disease of Bone.Frontiers in cell and developmental biology · 2022Article
- Ras and Rab Interactor 3: From Cellular Mechanisms to Human Diseases.Frontiers in cell and developmental biology · 2022Review
- Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation.Calcified tissue international · 2021Article
- Genetic Determinants of Paget's Disease of Bone.Current osteoporosis reports · 2021Review
- Rab GTPases in Osteoclastic Bone Resorption and Autophagy.International journal of molecular sciences · 2020Review
- Article
- MRLR: unraveling high-resolution meiotic recombination by linked reads.Bioinformatics (Oxford, England) · 2020Article
- Targeted sequencing ofBone reports · 2019Article
- Paget's Disease of Bone.Calcified tissue international · 2019Review
- Human Genetics of Sclerosing Bone Disorders.Current osteoporosis reports · 2018Review
- Screening Gene Knockout Mice for Variation in Bone Mass: Analysis by μCT and Histomorphometry.Current osteoporosis reports · 2018Review
- Rab GTPases in Osteoclastic Endomembrane Systems.BioMed research international · 2018Review
- The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping.Nature reviews. Rheumatology · 2017Review
- Clinical and Genetic Advances in Paget's Disease of Bone: a Review.Clinical reviews in bone and mineral metabolism · 2017Review
- Paget's disease of bone-genetic and environmental factors.Nature reviews. Endocrinology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Paget's disease of bone (PDB) is a common disorder with a strong genetic component characterized by increased but disorganized bone remodelling. Previous genome-wide association studies identified a locus on chromosome 14q32 tagged by rs10498635 which was significantly associated with susceptibility to PDB in several European populations. Here we conducted fine-mapping and targeted sequencing of the candidate locus to identify possible functional variants. Imputation in 741 PDB patients and 2699 controls confirmed that the association was confined to a 60 kb region in the RIN3 gene and conditional analysis adjusting for rs10498635 identified no new independent signals. Sequencing of the RIN3 gene identified a common missense variant (p.R279C) that was strongly associated with the disease (OR = 0.64; P = 1.4 × 10(-9)), and was in strong linkage disequilibrium with rs10498635. A further 13 rare missense variants were identified, seven of which were novel and detected only in PDB cases. When combined, these rare variants were over-represented in cases compared with controls (OR = 3.72; P = 8.9 × 10(-10)). Most rare variants were located in a region that encodes a proline-rich, intrinsically disordered domain of the protein and many were predicted to be pathogenic. RIN3 was expressed in bone tissue and its expression level was ∼10-fold higher in osteoclasts compared with osteoblasts. We conclude that susceptibility to PDB at the 14q32 locus is mediated by a combination of common and rare coding variants in RIN3 and suggest that RIN3 may contribute to PDB susceptibility by affecting osteoclast function.
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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.