孟德尔随机化研究探索骨坏死风险△

A Mendelian randomisation study to explore the risk of osteonecrosis

摘要:

[目的] 运用孟德尔随机化 （Mendelian randomization, MR） 研究探索多种危险因素与骨坏死之间的因果关联。[方法]暴露因素（吸烟、酗酒、肥胖、焦虑、抑郁、糖皮质激素）和结局事件（骨坏死）的单核苷酸多态性通过公开发表的全基因组关联分析（genome-wide association study, GWAS）数据库和芬兰基因生物库（FinnGen Biobank, FGB）开展研究。采用逆方差加权法 （inverse-variance weighted, IVW）、加权模型法 （weighted mode, WM） 和 MREgger 法进行检测和校对研究结果，并进行异质性检验、敏感性分析、多效性检验验证结果稳定性。[结果]IVW 结果表明，酗酒（OR=3.059, 95%CI: 1.080~8.665, P= 0.039）、抑郁 （OR=1.542, 95%CI: 1.050~2.264, P=0.027）、吸烟 （OR=1.379, 95%CI: 1.073~1.773, P=0.012）、糖皮质激素 （OR= 1.357, 95%CI: 1.046~1.760, P=0.021） 与骨坏死的风险呈显著正相关。而与肥胖和焦虑无显著相关性 （P＞0.05）。敏感性分析显示，结果稳定可靠，多效性检验显示不存在水平多效性。[结论]本研究结果表明，吸烟、酗酒、抑郁和糖皮质激素增加了骨坏死患病风险，而没有足够的证据表明肥胖和焦虑与骨坏死之间存在因果关联。

Abstract:

[Objective] A Mendelian randomization (MR) study was conducted to explore the causal association between multiple risk factors and osteonecrosis. [Methods] Relationship of the nucleotide polymorphisms of exposure factors, including smoking, alcohol abuse, obesity, anxiety, depression, glucocorticoids and outcome events (osteonecrosis) were investigated by means of publicly available genomewide association study (GWAS) databases and the FinnGen Biobank (FGB). The inverse-variance weighted (IVW) method, supplemented by the MREgger method, weighted median (WME), weighted mode (WM), and simple mode (SM), were used to testing and calibrating the results of the study. Heterogeneity test, sensitivity analysis, and multiple validity test were conducted to verify the stability of the results. [Results] As results of IVW, smoking (OR=1.379, 95%CI: 1.073~1.773, P=0.012), alcohol abuse (OR=3.059, 95%CI: 1.080~8.665, P=0.039), depression (OR=1.542, 95%CI: 1.050~2.264, P=0.027), and glucocorticoids (OR=1.357, 95%CI: 1.046~1.760, P=0.021) were positively and causally associated with the risk of osteonecrosis. The sensitivity analyses showed the consequence was stable and reliable, while the tests for multiplicity showed no horizontal pleiotropy. [Conclusion] The results of this study suggest that smoking, alcohol abuse, depression, and glucocorticoids increase the risk of developing osteonecrosis, whereas there is insufficient evidence of a causal association between obesity and anxiety and osteonecrosis.