Multiple anthropometric characteristics and Brugada syndrome: A Mendelian randomization study

Area of Science:

• Cardiovascular Genetics
• Metabolic Health
• Genetic Epidemiology

Background:

• Observational studies suggest Brugada syndrome (BrS) is linked to lower obesity rates and body mass index (BMI).
• The causal relationship between anthropometric traits and BrS risk remains unclear.

Purpose of the Study:

• To investigate the causal effects of genetically predicted anthropometric traits on the risk of Brugada syndrome using Mendelian randomization.
• To explore potential protective factors against BrS based on genetic predispositions.

Main Methods:

• Two-sample Mendelian randomization (MR) analyses were performed using genome-wide association study summary statistics.
• Inverse-variance weighted (IVW) method was primary, supported by MR-Egger and weighted median methods.
• Extensive sensitivity analyses were conducted to ensure result robustness.

Main Results:

• Genetically predicted higher comparative body size at age 10 was inversely associated with BrS risk (OR=0.40, P=2.07×10⁻⁵).
• Adult obesity (OR=0.78, P=1.42×10⁻⁴), childhood obesity, fat-free mass, BMI, waist-to-hip ratio, and basal metabolic rate showed potential protective effects.
• Reverse MR indicated genetically predicted BrS was associated with increased waist and hip circumference.

Conclusions:

• Genetically determined higher childhood/adult obesity and increased fat-free mass may confer a reduced risk of Brugada syndrome.
• Strategies like maintaining an upper-normal BMI and increasing fat-free mass through resistance training may help mitigate BrS risk.