Abstract：
OBJECTIVE: This study examines the causal relationships between serum micronutrients and site-specific osteoarthritis (OA) using Mendelian Randomization (MR).
METHODS: This study performed a two-sample MR analysis to explore causal links between 21 micronutrients and 11 OA outcomes. These outcomes encompass overall OA, seven site-specific manifestations, and three joint replacement subtypes. Sensitivity analyses using MR methods, such as the weighted median, MR-Egger, and MR-PRESSO, assessed potential horizontal pleiotropy and heterogeneity. Genome-wide association summary statistical data were utilized for both exposure and outcome data, including up to 826,690 participants with 177,517 OA cases. All data was sourced from Genome-wide association studies datasets from 2009 to 2023.
RESULTS: In the analysis of associations between 21 micronutrients and 11 OA outcomes, 15 showed Bonferroni-corrected significance (P < 0.000216), without significant heterogeneity or horizontal pleiotropy. Key findings include strong links between gamma-tocopherol and spine OA (OR = 1.70), and folate with hand OA in finger joints (OR = 1.15). For joint replacements, calcium showed a notable association with a reduced likelihood of total knee replacement (TKR) (OR = 0.52) and total joint replacement (TJR) (OR = 0.56). Serum iron was significantly associated with an increased risk of total hip replacement (THR) (OR = 1.23), while folate indicated a protective effect (OR = 0.95). Various sex-specific associations were also uncovered.
CONCLUSIONS: These findings underscore the critical role of micronutrients in osteoarthritis, providing valuable insights for preventive care and potential enhancement of treatment outcomes.
METHODS: This study performed a two-sample MR analysis to explore causal links between 21 micronutrients and 11 OA outcomes. These outcomes encompass overall OA, seven site-specific manifestations, and three joint replacement subtypes. Sensitivity analyses using MR methods, such as the weighted median, MR-Egger, and MR-PRESSO, assessed potential horizontal pleiotropy and heterogeneity. Genome-wide association summary statistical data were utilized for both exposure and outcome data, including up to 826,690 participants with 177,517 OA cases. All data was sourced from Genome-wide association studies datasets from 2009 to 2023.
RESULTS: In the analysis of associations between 21 micronutrients and 11 OA outcomes, 15 showed Bonferroni-corrected significance (P < 0.000216), without significant heterogeneity or horizontal pleiotropy. Key findings include strong links between gamma-tocopherol and spine OA (OR = 1.70), and folate with hand OA in finger joints (OR = 1.15). For joint replacements, calcium showed a notable association with a reduced likelihood of total knee replacement (TKR) (OR = 0.52) and total joint replacement (TJR) (OR = 0.56). Serum iron was significantly associated with an increased risk of total hip replacement (THR) (OR = 1.23), while folate indicated a protective effect (OR = 0.95). Various sex-specific associations were also uncovered.
CONCLUSIONS: These findings underscore the critical role of micronutrients in osteoarthritis, providing valuable insights for preventive care and potential enhancement of treatment outcomes.
摘要：
目的：本研究使用孟德尔随机化（MR）检查血清微量营养素与部位特异性骨关节炎（OA）之间的因果关系。
方法：本研究进行了双样本MR分析，以探讨21种微量营养素与11种OA结果之间的因果关系。这些结果包括整体OA，七个特定地点的表现，和三种关节置换亚型。使用MR方法进行敏感性分析，比如加权中位数，MR-Egger,和MR-PRESSO,评估潜在的水平多效性和异质性。全基因组关联汇总统计数据用于暴露和结果数据，包括多达826,690名参与者，包括177,517例OA病例。所有数据均来自2009年至2023年的全基因组关联研究数据集。
结果：在21种微量营养素与11种OA结果之间的关联分析中，15显示Bonferroni校正的显著性(P<0.000216)，没有显著的异质性或水平多效性。主要发现包括γ-生育酚与脊柱OA之间的紧密联系（OR=1.70），和叶酸与手指关节中的手OA（OR=1.15）。对于关节置换，钙与全膝关节置换(TKR)(OR=0.52)和全关节置换(TJR)(OR=0.56)的可能性降低显著相关.血清铁与全髋关节置换术（THR）风险增加显著相关（OR=1.23），叶酸有保护作用(OR=0.95)。还发现了各种性别特定的关联。
结论：这些发现强调了微量营养素在骨关节炎中的关键作用，为预防性护理和潜在的治疗结果增强提供有价值的见解。
方法：本研究进行了双样本MR分析，以探讨21种微量营养素与11种OA结果之间的因果关系。这些结果包括整体OA，七个特定地点的表现，和三种关节置换亚型。使用MR方法进行敏感性分析，比如加权中位数，MR-Egger,和MR-PRESSO,评估潜在的水平多效性和异质性。全基因组关联汇总统计数据用于暴露和结果数据，包括多达826,690名参与者，包括177,517例OA病例。所有数据均来自2009年至2023年的全基因组关联研究数据集。
结果：在21种微量营养素与11种OA结果之间的关联分析中，15显示Bonferroni校正的显著性(P<0.000216)，没有显著的异质性或水平多效性。主要发现包括γ-生育酚与脊柱OA之间的紧密联系（OR=1.70），和叶酸与手指关节中的手OA（OR=1.15）。对于关节置换，钙与全膝关节置换(TKR)(OR=0.52)和全关节置换(TJR)(OR=0.56)的可能性降低显著相关.血清铁与全髋关节置换术（THR）风险增加显著相关（OR=1.23），叶酸有保护作用(OR=0.95)。还发现了各种性别特定的关联。
结论：这些发现强调了微量营养素在骨关节炎中的关键作用，为预防性护理和潜在的治疗结果增强提供有价值的见解。
