母外翻与膝骨关节炎基因关系的孟德尔随机化研究△

A Mendelian randomized study of the genetic relationship between hallux valgus and knee osteoarthritis

摘要:

[目的]采用双向两样本孟德尔随机化研究探讨母外翻和膝骨关节炎之间的因果关系。[方法]基于全基因组关联研究（genome-wide association study, GWAS）数据库，应用逆方差加权（inverse-variance weighted，IVW）、加权众数法（weighted mode） 和 MR-Egger 进行双向两样本孟德尔随机化研究分析。[结果]母外翻是膝骨关节炎发生的危险因素，IVW 结果（OR= 1.14, P=0.015）；膝骨关节炎也是母外翻发生的危险因素，IVW 结果（OR=1.65, P=1.51e-05）。双向两样本孟德尔随机化研究中均没有水平多效性的存在（P＞0.05）。“留一法”分析显示，双向两样本孟德尔随机化研究的结果都是可靠的。[结论] 从大样本和遗传学角度上来看，母外翻是膝骨关节炎风险增加的危险因素，膝骨关节炎同样是母外翻风险增加的危险因素，且两结果之间具有独立性和可靠性。

Abstract:

[Objective] A bidirectional two-sample Mendelian randomization study was conducted to investigate the causal relationship between hallux valgus and knee osteoarthritis. [Methods] Based on GWAS (Genome-wide Association Study) database, IVW (inverse-variance weighted), weighted mode and MR-Egger were used to conduct bidirectional two-sample Mendelian randomization analysis. [Results] There was a positive causal relationship between hallux valgus and increased risk of knee osteoarthritis, with IVW (OR=1.14, 95%CI: 1.03~ 1.27, P=0.015). There was also a positive causal relationship between knee osteoarthritis and increased risk of hallux valgus with IVW (OR= 1.65, 95%CI: 1.31~2.06, P＜0.001). There was no horizontal pleiotropy in the bidirectional two-sample Mendelian randomization study (P＞ 0.05). The results of bidirectional twosample Mendelian randomization are robust. [Conclusion] From a large sample size and genetics, hallux valgus is a risk factor for knee osteoarthritis. On other hand, knee osteoarthritis is also a risk factor for hallux valgus, and there is independence and stability between the two outcomes.