基于两样本孟德尔随机化的肺功能与新型冠状病毒肺炎病死风险的因果关系

doi:10.6040/j.issn.1671-7554.0.2021.0241

摘要/Abstract

摘要： 目的采用两样本孟德尔随机化方法探索肺功能与新型冠状病毒肺炎(COVID-19)病死风险之间的因果关联。方法对基于全基因关联研究(GWAS)的汇总数据进行二次数据分析。利用大样本GWAS汇总数据,选择与肺功能密切关联的遗传位点作为工具变量,分别用逆方差加权法、MR-Egger回归和加权中位数法做两样本孟德尔随机化分析,以OR值评价肺功能与COVID-19病死风险之间的因果关系。结果共纳入287个单核苷酸多态性作为工具变量,MR-Egger回归结果表明基因多效性不会对结果造成偏倚(P=0.107)。逆方差加权法结果显示,肺功能每增加一个标准差,会导致COVID-19患者病死风险降低62%(OR=0.38, 95%CI: 0.18~0.80)。MR-Egger回归也得到了相似的结果(OR=0.08, 95%CI: 0.01~0.61)。加权中位数法结果显示肺功能与COVID-19病死风险之间关联无统计学意义(OR=0.44, 95%CI: 0.14~1.42)。结论肺功能与COVID-19病死风险之间可能存在负向因果关联。

关键词: 孟德尔随机化, 肺功能, 新型冠状病毒肺炎, 因果推断

Abstract: Objective To investigate whether lung function was causally associated with risk of fatality of COVID-19 based on a two-sample Mendelian randomization study. Methods This two-sample Mendelian randomization study used summary-level datasets of genome-wide association studies(GWAS)of forced vital capacity(FVC)and risk of fatality of COVID-19 from the UK Biobank. Inverse-variance weighted(IVW), MR-Egger regression, and weighted median estimator(WME)were conducted to investigate the association of lung function with risk of fatality of COVID-19, in which the OR values were used as indicators. Results A total of 287 single nucleotide polymorphisms were enrolled as instrumental variables. Statistically significant directional pleiotropy was not found(P=0.107). IVW regression demonstrated that per 1 elevated SD of FVC resulted in decreasing 62% of fatality risk in COVID-19 patients(OR=0.38, 95%CI: 0.18-0.80). MR-Egger regression also obtained a similar effect(OR=0.08, 95%CI: 0.01-0.61). WME analysis showed no significant association of FVC with risk of fatality of COVID-19(OR=0.44, 95%CI: 0.14-1.42). Conclusion Lung function might be negatively related to risk of fatality of COVID-19.

Key words: Mendelian randomization, Lung function, COVID-19, Causality inference

中图分类号:

R563.1

杨璇,李岩志,马伟,贾崇奇. 基于两样本孟德尔随机化的肺功能与新型冠状病毒肺炎病死风险的因果关系[J]. 山东大学学报 (医学版), 2021, 59(7): 104-111.

YANG Xuan, LI Yanzhi, MA Wei, JIA Chongqi. Causal influence of lung function on risk of fatality of COVID-19: a two-sample Mendelian randomization study[J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 104-111.

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