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Assessing causality between different risk factors and pulmonary embolism: A Mendelian randomization study
Jian-Ming Wei1, Yan-Li Song1, Huan Zeng1
1Department of Emergency Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Objectives:
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.
Methods:
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.
Results:
In the IVW model, genetically elevated BMI was causally associated with PE [OR = 1.002, 95% CI (1.001, 1004), P = 0.039]. Cochran's Q test was used to detect heterogeneity in the MR-Egger analysis (P = 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 (P = 0.926).
Conclusion:
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.
Insights
Body mass index (BMI) causally increases the risk of pulmonary embolism (PE) in European populations. However, other factors like smoking, heart failure, alcohol intake, and inflammatory bowel disease (IBD) showed no direct causal link to PE.
Area of Science:
- Genetics and Epidemiology
- Cardiovascular Health
- Public Health
Background:
- Investigating causal links between various health factors and pulmonary embolism (PE) is crucial for understanding disease etiology.
- Previous observational studies suggest potential associations, but Mendelian randomization (MR) can establish causality.
Purpose of the Study:
- To determine the causal relationship between body mass index (BMI), smoking status, heart failure, alcohol intake frequency, inflammatory bowel disease (IBD), and PE using MR.
- To assess whether genetic predisposition to these factors influences PE risk.
Main Methods:
- Utilized Mendelian randomization (MR) with pooled data from large-scale Genome-Wide Association Study (GWAS) meta-analyses.
- Employed inverse variance weighted (IVW), weighted median (WM), and MR-Egger methods for primary analysis.
- Validated findings using multivariate MR to account for potential confounders.
Main Results:
- Genetically elevated BMI was causally associated with an increased risk of PE (IVW OR = 1.002, P = 0.039).
- No significant causal associations were found between PE and ever smoking, heart failure, IBD, or alcohol intake frequency.
- Multivariate MR analysis confirmed no causal effect of BMI on PE when considering height and weight.
Conclusions:
- A causal relationship exists between higher BMI and increased PE risk in European ancestry populations.
- Factors such as smoking, heart failure, alcohol intake, and IBD do not appear to have a direct causal effect on PE.
- The findings highlight BMI as a modifiable risk factor for PE.
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