Department of Medical Sciences, University of Turin, Turin, Italy.
Italian Institute for Genomic Medicine, IIGM, Turin, Italy.
Ann Rheum Dis. 2018 Apr;77(4):620-623. doi: 10.1136/annrheumdis-2017-211848. Epub 2018 Feb 7.
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.
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.
We detect a genome-wide significant association at rs10116772 with TJR (P=3.7×10; for allele A: OR (95% CI) 0.97 (0.96 to 0.98)), an intronic variant in , which is expressed in cartilage. Variants in strong correlation with rs10116772 have been associated with elevated plasma glucose levels and diabetes.
We identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.
骨关节炎（OA）是一种复杂的疾病，但遗传病因仍未得到充分描述。为了确定 OA 的新易感基因座，我们对迄今为止英国最大的 OA 样本中个体进行了全基因组关联研究（GWAS）。
我们对 5414 名膝关节和/或髋关节全关节置换术（TJR）OA 患者和 9939 名基于人群的对照者进行了发现 GWAS。我们对来自英国生物银行资源中期发布的 OA 患者（最多 12658 例和 50898 例对照者）和我们在英国生物银行全发布中对手术 OA 患者的优先变异体进行了随访（17894 例和 89470 例对照者）。我们在来自接受 TJR 的 12 对完整和降解软骨样本的原代软骨细胞的甲基化、基因表达和蛋白质组学数据中研究了其功能意义。
我们在 TJR 中检测到与 rs10116772 具有全基因组显著关联（P=3.7×10；等位基因 A：OR（95%CI）0.97（0.96 至 0.98）），这是一种在软骨中表达的 内含子变体。与 rs10116772 强相关的变体与升高的血浆葡萄糖水平和糖尿病有关。
我们确定了一个新的 OA 易感基因座，该基因座先前与糖尿病和血糖特征有关。
