A novel variant in GLIS3 is associated with osteoarthritis

Publication type

Journal Article

Published in

Annals of the Rheumatic Diseases

Authors

Elisabetta Casalone, Ioanna Tachmazidou, Eleni Zengini, Konstantinos Hatzikotoulas, Sophie Hackinger, Dániel Süveges, Julia Steinberg, Nigel William Rayner, Jeremy Mark Wilkinson, Kalliope Panoutsopoulou and Eleftheria Zeggini

Publication date

Summary

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.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.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.Conclusions: We identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.

Volume and page numbers

77, 620-623

DOI

https://dx.doi.org/10.1136/annrheumdis-2017-211848

ISSN

16

Subjects

Medicine, Science And Technology, Health and Genetics

Notes

Open Access; This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/