髋或膝骨关节炎与衰弱之间的遗传因果关联:一项两样本孟德尔随机化分析。
The genetic causal association between hip or knee osteoarthritis and frailty: a two-sample Mendelian randomization analysis.
作者信息
Zhou Jinlei, Li Yanlei, Lin Yanze, Wang Fei, Tian Jinlong, Wang Yongguang, Bi Qing, Wang Changxing, Zhao Tingxiao
机构信息
Center for Plastic and Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
出版信息
Arch Med Sci. 2024 Apr 25;20(3):938-946. doi: 10.5114/aoms/176741. eCollection 2024.
INTRODUCTION
Osteoarthritis of the hip or knee has been reported to be linked to an increased risk of frailty. However, a definitive conclusion about whether hip or knee osteoarthritis increases susceptibility to frailty remains elusive.
MATERIAL AND METHODS
The instrumental variables (IVs) used in this analysis were sourced from publicly available genome-wide association study (GWAS) datasets. We used a two-sample Mendelian randomization analysis to evaluate the plausible causal nexus between hip or knee osteoarthritis and frailty.
RESULTS
We included a total of 25 single-nucleotide polymorphisms (SNPs) as instrumental variables through rigorous and comprehensive screening. The results of this analysis suggested that hip or knee osteoarthritis is associated with an elevated risk of frailty. These results remained robust and consistent across multiple calculation methods, including inverse variance weighted (OR = 1.082, 95% CI: 1.0532-1.1125, = 1.36 × 10), MR-Egger regression (OR = 1.175, 95% CI: 1.0162-1.3604, = 0.040), weighted median estimation (OR = 1.078, 95% CI: 1.0365-1.1219, = 1.831 × 10), weighted mode analysis (OR = 1.089, 95% CI: 1.0078-1.1771, = 0.041) and simple mode analysis (OR = 1.093, 95% CI: 1.0112-1.1830, = 0.034). Cochran's Q test showed no evidence of heterogeneity among the IV estimates derived from individual variants, and the MR-Egger regression analysis indicated that the presence of horizontal pleiotropy was unlikely to introduce bias into the results (intercept: -0.0044, = 0.549).
CONCLUSIONS
Two-sample Mendelian randomization analysis effectively identified hip or knee osteoarthritis as a contributing risk factor for frailty.
引言
据报道,髋部或膝部骨关节炎与衰弱风险增加有关。然而,关于髋部或膝部骨关节炎是否会增加衰弱易感性的明确结论仍不明确。
材料与方法
本分析中使用的工具变量(IVs)来自公开可用的全基因组关联研究(GWAS)数据集。我们使用两样本孟德尔随机化分析来评估髋部或膝部骨关节炎与衰弱之间可能的因果关系。
结果
通过严格全面的筛选,我们共纳入了25个单核苷酸多态性(SNPs)作为工具变量。该分析结果表明,髋部或膝部骨关节炎与衰弱风险升高有关。这些结果在多种计算方法中都保持稳健且一致,包括逆方差加权法(OR = 1.082,95% CI:1.0532 - 1.1125,P = 1.36 × 10)、MR - Egger回归法(OR = 1.175,95% CI:1.0162 - 1.3604,P = 0.040)、加权中位数估计法(OR = 1.078,95% CI:1.0365 - 1.1219,P = 1.831 × 10)、加权模式分析法(OR = 1.089,95% CI:1.0078 - 1.1771,P = 0.041)和简单模式分析法(OR = 1.093,95% CI:1.0112 - 1.1830,P = 0.034)。Cochran's Q检验显示,来自各个变体的IV估计值之间没有异质性证据,并且MR - Egger回归分析表明,水平多效性的存在不太可能给结果带来偏差(截距:-0.0044,P = 0.549)。
结论
两样本孟德尔随机化分析有效地确定了髋部或膝部骨关节炎是衰弱的一个促成风险因素。