双向两样本孟德尔随机化分析失眠与心肌梗死的因果关系

Bidirectional two-sample Mendelian randomization study of insomnia and myocardial infarction

[目的]采用双向两样本孟德尔随机化(MR)分析失眠与心肌梗死(MI)之间的关联。[方法]从全基因组关联研究(GWAS)中获取MI的遗传关联数据,选择失眠表型相关的单核苷酸多态性(SNP)作为工具变量。以逆方差加权法(IVW)为主要方法评估失眠与MI之间的因果关系。[结果] MR分析表明,失眠与MI发病存在正向关联[IVW:优势比(OR)=1.015,95%可信区间(CI)1.004~1.027,P=0.007],工具变量不存在水平多效性与异质性,敏感性分析提示MR分析结果稳定。反向MR分析提示MI与失眠风险增加之间无因果关系(IVW:OR=0.725,95%CI 0.466~1.126,P=0.152),去除离群值之后统计结果稳定。[结论]失眠是MI的危险因素,失眠与MI发病存在正向关联。但MI与失眠风险增加不存在因果关系。

Aim To explore the association between insomnia and myocardial infarction(MI)using bidirectional two-sample Mendelian randomization(MR).Methods The summary statistics of MI were obtained from genome-wide association studies(GWAS),and single nucleotide polymorphisms(SNP)associated with insomnia phenotype were selected as instrumental variables.Inverse variance weighting(IVW)was used to evaluate the causal relationship between insomnia and MI.Results MR analysis showed that there was positive relationship between insomnia and MI(IVW:OR=1.015,95%CI 1.004~1.027,P=0.007).There was no horizontal pleiotropy and heterogeneity in instrumental variables.Sensitivity analysis suggested that MR analysis results were stable.Reverse MR analysis showed no causal relationship between MI and increased risk of insomnia(IVW:OR=0.725,95%CI 0.466~1.126,P=0.152),and the statistical results were stable after the removal of outliers.Conclusion Insomnia is a risk factor for MI and there was positive relationship between insomnia and MI.However,there was no causal relationship between MI and an increased risk of insomnia.