| Title: | A novel variant in GLIS3 is associated with osteoarthritis |
| Journal: | Annals of the Rheumatic Diseases |
| Published: | 7 Feb 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29436472/ |
| DOI: | https://doi.org/10.1136/annrheumdis-2017-211848 |
| URL: | https://ard.bmj.com/content/annrheumdis/77/4/620.full.pdf |
| Citations: | 31 (5 in last 2 years) as of 8 Aug 2024 |
Publication 3920
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Abstract
OBJECTIVES: Osteoarthritis (OA) is a complex disease, but its genetic aetiology remains poorly characterised. To identify novel susceptibility loci for OA, we carried out a genome-wide association study (GWAS) in individuals from the largest UK-based OA collections to date.</p>
METHODS: We carried out a discovery GWAS in 5414 OA individuals with knee and/or hip total joint replacement (TJR) and 9939 population-based controls. We followed-up prioritised variants in OA subjects from the interim release of the UK Biobank resource (up to 12 658 cases and 50 898 controls) and our lead finding in operated OA subjects from the full release of UK Biobank (17 894 cases and 89 470 controls). We investigated its functional implications in methylation, gene expression and proteomics data in primary chondrocytes from 12 pairs of intact and degraded cartilage samples from patients undergoing TJR.</p>
RESULTS: We detect a genome-wide significant association at rs10116772 with TJR (P=3.7×10-8; for allele A: OR (95% CI) 0.97 (0.96 to 0.98)), an intronic variant in GLIS3, which is expressed in cartilage. Variants in strong correlation with rs10116772 have been associated with elevated plasma glucose levels and diabetes.</p>
CONCLUSIONS: We identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.</p>
27 Authors
- Elisabetta Casalone
- Ioanna Tachmazidou
- Eleni Zengini
- Konstantinos Hatzikotoulas
- Sophie Hackinger
- Daniel Suveges
- Julia Steinberg
- Nigel William Rayner
- arcOGEN Consortium
- Jeremy Mark Wilkinson
- Kalliope Panoutsopoulou
- Eleftheria Zeggini
- John Loughlin
- Nigel Arden
- Fraser Birrell
- Andrew Carr
- Panos Deloukas
- Michael Doherty
- Andrew W McCaskie
- William E R Ollier
- Ashok Rai
- Stuart H Ralston
- Tim D Spector
- Ana M Valdes
- Gillian A Wallis
- Jeremy Mark Wilkinson
- Eleftheria Zeggini
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