Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013–1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014–1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003–1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018–1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022–1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000–1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014–1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.

中文翻译：

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循环细胞因子水平和骨关节炎：孟德尔随机研究

先前的传统观察性研究表明，多种细胞因子和生长因子对骨关节炎（OA）的发展有贡献。本研究旨在确定循环细胞因子和生长因子水平与 OA 的关系。我们使用两个样本孟德尔随机化 (MR) 来探讨循环细胞因子和生长因子水平与 OA [包括膝关节或髋关节 OA (K/HOA)、膝关节 OA (KOA) 和髋关节 OA (HOA)] 之间的因果关系。循环细胞因子和生长因子水平的汇总水平数据源自一项全基因组关联研究 (GWAS)，该研究涉及 8,293 名芬兰血统参与者。从之前的 GWAS 中获得了与 K/HOA（39,427 例病例和 378,169 对照）、KOA（24,955 例病例和 378,169 对照）和 HOA（15,704 例病例和 378,169 对照）相关的单核苷酸多态性。逆方差加权 (IVW) 方法主要用于我们的 MR 分析。对于仅暴露于一种相关 SNP 作为 IV 的情况，我们使用 Wald 比率作为评估因果效应的主要方法。我们还进行了一系列敏感性分析，以提高结果的稳健性。循环血管内皮生长因子水平与 K/HOA 风险增加相关（优势比 (OR) = 1.034；95% 置信区间 (CI) = 1.013–1.055；P = 0.001）、KOA（OR = 1.034；95） % CI = 1.014–1.065；P = 0.002）和 HOA（OR = 1.039；95 % CI = 1.003–1.067；P = 0.034）。循环白介素 (IL)-12p70 水平提示与 K/HOA（OR = 1.047；95% CI = 1.018–1.077；P = 0.001）、KOA（OR = 1.058；95% CI = 1.022–1.095；P = 0.001）相关）和 HOA（OR = 1.044；95% CI = 1.000–1.091；P = 0.048）。循环 IL-18 水平与 HOA 相关（OR = 1.068；95% CI = 1.014–1.125；P = 0.012）。然而，支持其他循环细胞因子、生长因子水平和 K/HOA、KOA 和 HOA 之间因果遗传关系的证据有限。我们的 MR 分析提供了循环细胞因子和生长因子水平与 OA 之间因果关系的提示性证据，为 OA 病因学提供了新的见解。