期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 77, 期 4, 页码 620-622出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2017-211848
关键词
osteoarthritis; genome-wide association study; functional genomics; single nucleotide polymorphism
类别
资金
- Medical Research Council [G1001799, MC_QA137853, MR/P020941/1, MR/N01104X/2, MR/N01104X/1] Funding Source: Medline
- Versus Arthritis [20308] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- ESRC [ES/S008349/1] Funding Source: UKRI
- MRC [MR/P020941/1, MR/N01104X/1, MR/N01104X/2, G1001799] Funding Source: UKRI
- Economic and Social Research Council [ES/S008349/1] Funding Source: researchfish
- Medical Research Council [MR/N01104X/2, G1001799, MR/N01104X/1, MR/P020941/1, MC_qA137853] Funding Source: researchfish
- Versus Arthritis [20308] Funding Source: researchfish
- Wellcome Trust [213422/Z/18/Z] Funding Source: researchfish
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 12658 cases and 50898 controls) and our lead finding in operated OA subjects from the full release of UK Biobank (17894 cases and 89470 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=3.7x10(-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.
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