Assessing causality between different risk factors and pulmonary embolism: A Mendelian randomization study.

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.