Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.
Semin Arthritis Rheum. 2022 Aug;55:152030. doi: 10.1016/j.semarthrit.2022.152030. Epub 2022 May 24.
Osteoarthritis (OA) is a progressive disease for which there is no disease modifying therapy. Vitamin K levels and vitamin K antagonism have been associated with risk and progression of OA which may have direct implications for clinical management, but these observational findings are susceptible to confounding. We aimed to estimate the causal association between vitamin K and OA risk using Mendelian randomisation (MR).
We used data from the largest genome-wide association study (GWAS) of OA to date (up to 826,690 individuals) to estimate the effect of genetically predicted vitamin K level (instrumented using four variants derived from a GWAS of 2,138 individuals) on risk of all OA types, knee, hip, spine, hand OA, and total joint replacement. We employed the inverse-variance weighted method for the primary analysis and, in a series of sensitivity analyses, adjusted for sub-genome wide significant instruments and tested for potential bias from pleiotropy.
We showed that genetically predicted vitamin K levels were not causally associated with risk of OA overall (OR 0.98 per unit increase in log-transformed vitamin K1; 95%CI 0.96-1.01), knee (OR 0.98; 0.92-1.03), hip (OR 0.97; 0.88-1.07), spine (OR 0.97; 0.90-1.04), hand OA (OR 0.97; 0.91-1.04) or joint replacement (OR 0.96; 0.89-1.04). Results were similar across all sensitivity analyses.
We found little evidence of a causal association between genetically predicted vitamin K and OA risk. Larger genetic and interventional studies of vitamin K are required to confirm our findings.
骨关节炎（OA）是一种进行性疾病，目前尚无治疗方法。维生素 K 水平和维生素 K 拮抗剂与 OA 的风险和进展有关，这可能对临床管理有直接影响，但这些观察性发现容易受到混杂因素的影响。我们旨在使用孟德尔随机化（MR）来估计维生素 K 与 OA 风险之间的因果关系。
我们使用迄今为止最大的 OA 全基因组关联研究（GWAS）的数据（多达 826690 人）来估计遗传预测的维生素 K 水平（通过来自对 2138 人的 GWAS 的四个变体来构建工具）对所有 OA 类型、膝关节、髋关节、脊柱、手部 OA 和全关节置换的风险的影响。我们采用逆方差加权法进行主要分析，并在一系列敏感性分析中，对亚基因组范围内具有显著意义的工具进行了调整，并测试了来自多效性的潜在偏差。
我们表明，遗传预测的维生素 K 水平与 OA 总体风险（每单位增加的维生素 K1 的对数变换的 OR 为 0.98；95%CI 0.96-1.01）、膝关节（OR 0.98；0.92-1.03）、髋关节（OR 0.97；0.88-1.07）、脊柱（OR 0.97；0.90-1.04）、手部 OA（OR 0.97；0.91-1.04）或关节置换（OR 0.96；0.89-1.04）之间没有因果关系。所有敏感性分析的结果均相似。
我们发现遗传预测的维生素 K 与 OA 风险之间几乎没有因果关系的证据。需要更大的遗传和干预性维生素 K 研究来证实我们的发现。
