超重与髋骨性关节炎基因关系的孟德尔法研究△

Mendelian method study on genetic relationship between overweight and hip osteoarthritis

摘要:

[目的] 采用孟德尔随机化 （Mendelian randomization, MR） 的方法，探讨超重与髋关节骨关节炎风险之间的因果关系，以期为临床防治提供理论依据。[方法]使用全基因组关联分析（genome-wide association study, GWAS）的公开数据开展研究，以超重作为暴露因素，以髋关节骨关节炎作为结局因素，提取与超重相关的工具变量 （instrumental variable, IV）。采用逆方差加权法 （inverse-variance weighted, IVW） 为主的 MR 方法。此外，使用 MR-Egger 法、加权中位数法 （weighted median, WME）、加权模型法 （weighted mode, WM） 和简单众数法 （simple mode, SM） 补充验证研究结果。并对实验结果进行异质性检验、敏感性分析和多效性分析。[结果]IVW 结果显示，超重与髋关节骨性关节炎呈正性相关关系（OR=1.720, 95% CI 1.320~ 2.250; P=6.23942E-05＜0.01)；MR-Egger 分析结果提示本研究不存在多效性（P=0.503）；Cochran's Q 检验结果 P=0.540，提示本研究结果不存在异质性；留一法检测分析依次剔除每个用于 MR 分析的单核苷酸多样性（single nucleotide polymorphisms, SNP）， 表明单个 SNP 不能明显影响总体的有效性，说明本研究结果稳定法可靠。[结论]超重和髋关节骨关节炎之间存在因果关系。

Abstract:

[Objective] Mendelian randomization (MR) method was used to investigate the causal relationship between overweight and hip osteoarthritis, in order to provide theoretical basis for clinical prevention and treatment. [Methods] Using publicly available data from the Genome-wide association study (GWAS), overweight as an exposure factor and hip osteoarthritis as an outcome factor, instrumental variable (IV) related to overweight was extracted. The MR method based on inverse-variance weighted (IVW) method was the main research method. In additon, the MR-Egger method, weighted median (WME) method and weighted mode (WM) method and simple mode method (SM) was used to verify the results. Furthermore, the results were tested for heterogeneity, sensitivity and pleiotropy. [Results] IVW results showed that overweight was positively correlated with hip osteoarthritis (OR=1.720, 95% CI 1.320~2.250; P=6.23942E-05, ＜0.01). The result of MR-Egger analysis suggested that there was no pleiotropy in this study (P=0.503). The results of Cochran's Q test (P=0.540) suggested that there is no heterogeneity in the results of this study. The single nucleotide polymorphisms (SNPS) used for MR Analysis were removed successively, which indicated that a single SNP could not significantly affect the overall effectiveness, indicating that results of this study were stable and reliable. [Conclusion] There is a causal relationship between overweight and hip osteoarthritis.