目的 分析虚弱症与骨性关节炎之间是否具有因果关系。方法 从2021年发表的全基因组关联研究（GWAS）汇总数据中获取并筛选出与虚弱症密切关联的工具变量,从芬兰数据库中筛选骨性关节炎、膝关节骨性关节炎的GWAS数据。运用两样本孟德尔随机化（MR）分析评估虚弱症与骨性关节炎、膝关节骨性关节炎之间的关联,并对结果进行敏感性分析。结果 筛选出与虚弱症显著相关的单核苷酸多态性位点（SNP）24个,与骨性关节炎显著相关的SNP 16个,与膝关节骨性关节炎显著相关的SNP 16个。在虚弱症作为暴露、骨性关节炎作为结局变量时,使用IVW法、Weighted median法均显示虚弱症与骨性关节炎风险增加相关（P<0.05）,敏感性检测显示存在异质性（P<0.05）,不存在水平多效性;在虚弱症作为暴露、膝关节骨性关节炎作为结局变量时,使用IVW法、Weighted median法均显示虚弱症与膝关节骨性关节炎风险增加相关（P<0.05）,敏感性检测显示存在异质性（P<0.05）,不存在水平多效性。结论 虚弱症可以增加患者罹患骨性关节炎的风险。
Abstract
Objective To analyze the causal relationship between frailty syndrome and osteoarthritis. Methods From the aggregated data of genome-wide association studies (GWAS) published in 2021, tool variables closely related to frailty syndrome were obtained and screened. GWAS data for osteoarthritis and knee osteoarthritis from the Finnish database were selected. Two-sample Mendelian randomization (MR) analysis was used to evaluate the association between frailty syndrome and osteoarthritis, knee osteoarthritis, and to conduct sensitivity analysis. Results A total of 24 SNPs were identified as significantly associated with frailty syndrome, 16 SNPs as significantly associated with osteoarthritis, and 16 SNPs as significantly associated with knee osteoarthritis. When frailty syndrome was the exposure and osteoarthritis was the outcome variable, the IVW method and the Weighted median method both showed that frailty syndrome was associated with an increased risk of osteoarthritis (P < 0.05), and sensitivity analysis showed heterogeneity (P < 0.05), but no horizontal pleiotropy; when frailty syndrome was the exposure and knee osteoarthritis was the outcome variable, the IVW method and the Weighted median method both showed that frailty syndrome was associated with an increased risk of knee osteoarthritis (P < 0.05), and sensitivity analysis showed heterogeneity (P < 0.05), but no horizontal pleiotropy. Conclusions Frailty syndrome can increase the risk of patients developing osteoarthritis.
关键词
虚弱症 /
骨关节炎 /
因果关系 /
孟德尔随机化
Key words
frailty syndrome /
osteoarthritis /
causal relationship /
Mendelian randomization
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