Wei Jian-Ming, Song Yan-Li, Zeng Huan, Yan Wen-Wen, Liu Xue-Bo
Department of Emergency Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2023 Feb 23;10:1057019. doi: 10.3389/fcvm.2023.1057019. eCollection 2023.
Mendelian randomization (MR) was used to estimate the causal relationship between body mass index (BMI), ever smoked, heart failure, alcohol intake frequency, inflammatory bowel disease (IBD), and pulmonary embolism (PE). This study aimed to investigate whether there is a causal relationship between BMI, the presence of smoking, heart failure, frequency of alcohol intake, IBD, and PE.
Pooled data on PE from a published GWAS meta-analysis involving approximately 461,164 participants of European ancestry were selected. A publicly available pooled dataset of BMI (461,460), ever smokers (461,066), heart failure (977,323), IBD (75,000), and frequency of alcohol intake (462,346) was used from another independent GWAS. MR was performed using established analysis methods, including Wald ratios, inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Also, the final expansion was validated with multivariate MR.
In the IVW model, genetically elevated BMI was causally associated with PE [OR = 1.002, 95% CI (1.001, 1004), = 0.039]. Cochran's test was used to detect heterogeneity in the MR-Egger analysis ( = 0.576). Therefore, the effect of gene-level heterogeneity was not considered. In the MR analysis of other risk factors, we observed genes for ever smoking [IVW OR = 1.004, 95% CI (0.997, 1.012)], heart failure [IVW OR = 0.999, 95% CI (0.996, 1.001)], IBD [IVW OR = 1.000, 95% CI (0.999, 1.001)], and frequency of alcohol intake [IVW OR = 1.002, 95% CI (1.000, 1.004)] were not causally associated with PE. Analysis using multivariate MR expansion showed no causal effect of BMI on PE considering the effect of height as well as weight ( = 0.926).
In European populations, a causal relationship exists between BMI and PE: increased BMI leads to PE. In contrast, ever smoking, heart failure, frequency of alcohol intake, and IBD are not directly associated with PE. There was no causal effect of BMI with PE in multivariate Mendelian randomized analysis.
采用孟德尔随机化（MR）方法估计体重指数（BMI）、既往吸烟情况、心力衰竭、饮酒频率、炎症性肠病（IBD）和肺栓塞（PE）之间的因果关系。本研究旨在探讨BMI、吸烟状态、心力衰竭、饮酒频率、IBD和PE之间是否存在因果关系。
从一项已发表的全基因组关联研究（GWAS）荟萃分析中选取了关于PE的汇总数据，该分析涉及约461,164名欧洲血统参与者。使用了另一个独立GWAS中公开可用的BMI（461,460）、既往吸烟者（461,066）、心力衰竭（977,323）、IBD（75,000）和饮酒频率（462,346）的汇总数据集。采用既定的分析方法进行MR分析，包括Wald比率、逆方差加权（IVW）、加权中位数（WM）和MR-Egger方法。此外，通过多变量MR对最终结果进行验证。
在IVW模型中，基因水平升高的BMI与PE存在因果关联[比值比（OR）=1.002，95%置信区间（CI）（1.001，1.004），P = 0.039]。在MR-Egger分析中，使用 Cochr an's Q检验检测异质性（P = 0.576）。因此，未考虑基因水平异质性的影响。在对其他危险因素的MR分析中，我们观察到既往吸烟[IVW OR = 1.004，95% CI（0.997，1.012）]、心力衰竭[IVW OR = 0.999，95% CI（0.996，1.001）]、IBD[IVW OR = 1.000，95% CI（0.999，1.001）]和饮酒频率[IVW OR = 1.002，95% CI（1.000，1.004）]与PE无因果关联。考虑身高和体重影响的多变量MR扩展分析显示，BMI对PE无因果效应（P = 0.926）。
在欧洲人群中，BMI与PE之间存在因果关系：BMI升高会导致PE。相比之下，既往吸烟、心力衰竭、饮酒频率和IBD与PE无直接关联。在多变量孟德尔随机化分析中，BMI对PE无因果效应。
