Multiple anthropometric measures and proarrhythmic 12-lead ECG indices: A mendelian randomization study

Area of Science:

• Cardiovascular Genetics
• Obesity Research
• Electrocardiography

Background:

• Observational studies suggest links between obesity and ECG indices, but causal inference is limited by confounding.
• Mendelian randomization (MR) is a powerful tool to investigate causal relationships between anthropometric measures and ECG parameters.
• Understanding these relationships is crucial for assessing arrhythmic risk associated with obesity.

Purpose of the Study:

• To explore the causal relevance of multiple anthropometric measures on key electrocardiogram (ECG) indices.
• To investigate the impact of body mass index (BMI), waist:hip ratio (aWHR), height, weight, fat mass, and fat-free mass on P-wave duration (PWD), PR interval, QRS duration, and corrected QT interval (QTc).
• To establish causal links between obesity-related traits and cardiac electrical activity.

Main Methods:

• Utilized Mendelian randomization (MR) with genome-wide association study (GWAS) data from large European ancestry cohorts (up to 806,834 individuals for BMI).
• Extracted genetic variants (SNPs) associated with anthropometric measures and ECG outcomes.
• Employed inverse-variance weighted MR as the primary analysis, with weighted median MR and MR-Egger as sensitivity analyses.

Main Results:

• Higher genetically predicted BMI, fat mass, fat-free mass, height, and weight were associated with longer P-wave duration (PWD).
• Genetically predicted BMI was associated with a longer corrected QT interval (QTc), driven by both fat mass and fat-free mass.
• Height, weight, and aWHR were also associated with a longer QTc interval.

Conclusions:

• This MR study provides evidence for a causal role of BMI in influencing multiple ECG indices linked to atrial and ventricular arrhythmic risk.
• The findings highlight the significant contributions of both fat mass and fat-free mass to these associations.
• Genetically predicted height also plays a role in the observed associations with ECG parameters.