便秘与肺炎因果关系的双向孟德尔随机化分析

Bidirectional Mendelian Randomization Analysis of Causal Relationship Between Constipation and Pneumonia

摘要:

目的 通过双向、双样本孟德尔随机化（MR）分析探讨便秘与肺炎之间的双向因果关系，从新的视角理解二者之间的潜在联系。方法 从全基因组关联研究（GWAS）网站选取便秘数据集和肺炎数据集，均为2021年欧洲人群。其中与便秘有关的数据包含411 623例样本，单核苷酸多态性（SNP）数据为24 176 599个；肺炎数据包含480 299例样本，SNP数量为24 174 646个。该研究采用逆方差加权法（IVW）作为MR的主要分析方法，以加权中位数法、简单模型、加权模型和MR-Egger回归法等分析结果为补充，并进行敏感性分析以评估结果的稳健性。结果 最终纳入17个与便秘高度相关的SNP，12个与肺炎高度相关的SNP。正向MR分析中，IVW分析结果显示，便秘可增加肺炎发生风险［比值比（OR）=1.143，95%置信区间（95%CI）［1.045，1.249］，P=0.003］；MR-Egger回归法、简单模型、加权模型、加权中位数分析均支持该结果（P<0.05）。反向MR分析的IVW分析结果显示，肺炎不会增加便秘的患病风险（OR=1.138，95%CI［0.974，1.329］，P=0.103）；MR-Egger回归法、简单模型、加权模型、加权中位数分析亦均支持该结果。结论 利用双向、双样本MR分析方法从遗传变异角度印证便秘与肺炎之间存在因果关系，反之则不存在明显因果关系。该研究将有助于对便秘与肺炎的临床诊疗，为二者之间发病机制研究提供参考。

Abstract:

Objective Bidirectional and two-sample Mendelian randomization（MR） method was used to investigate the bidirectional causal relationship between constipation and pneumonia and to understand the potential relationship between the two diseases from a new perspective， providing new targets for future treatment strategies.Method Constipation and pneumonia datasets were selected from the genome-wide association study（GWAS） website for the European population in 2021. The data related to constipation included 411 623 samples， and the single nucleotide polymorphism（SNP） data were 24 176 599. The pneumonia data contained 480 299 samples with a number of SNPs of 24 174 646. In this study， inverse variance weighting（IVW） was adopted as the main analysis method of MR， supplemented by weighted median method， simple model， weighted model and MR-Egger regression analysis results， and sensitivity analysis was performed to evaluate the robustness of the results.Result Seventeen SNPs highly correlated with constipation and 12 SNPs highly correlated with pneumonia were finally included. IVW analysis results of forward MR analysis showed that constipation increased the risk of pneumonia｛odds ratio（OR）=1.143， 95% confidence interval（CI）［1.045， 1.249］， P=0.003｝， MR-Egger regression， simple model， weighted model and weighted median analysis all supported the result（P<0.05）. IVW analysis by reverse MR analysis showed that pneumonia did not increase the risk of constipation｛OR=1.138， 95%CI［0.974， 1.329］， P=0.103｝， MR-Egger regression， simple model， weighted model and weighted median analysis also supported this result.Conclusion The bidirectional and dual-sample MR analysis method is used to confirm the causal relationship between constipation and pneumonia from the perspective of genetic variation， while there is no obvious causal relationship on the contrary. This study will be helpful for the clinical diagnosis and treatment of constipation and pneumonia， and provide a reference for the study of the pathogenesis between the two.