Estimating causality between smoking and abdominal obesity by Mendelian randomization

Area of Science:

• Genetics
• Obesity Research
• Public Health

Background:

• Smoking is linked to lower body weight but higher abdominal fat.
• The causal relationship between smoking and abdominal obesity is not fully understood.
• Previous studies using single genetic variants for smoking heaviness may yield imprecise causal estimates.

Purpose of the Study:

• To investigate the causal relationship between smoking and abdominal obesity using multiple genetic instruments.
• To differentiate the effects of smoking initiation, lifetime smoking, and smoking heaviness on abdominal fat distribution.

Main Methods:

• Utilized Mendelian randomization (MR) with Causal Analysis Using Summary Effect Estimates (CAUSE) and Latent Heritable Confounder MR (LHC-MR) methods.
• Employed genome-wide association studies (GWAS) summary statistics for smoking traits and abdominal obesity measures (waist-hip ratio, waist circumference, hip circumference).
• Included analyses with and without body mass index adjustment.

Main Results:

• Both CAUSE and LHC-MR indicated a positive causal effect of smoking initiation and lifetime smoking on waist-hip ratio, even after adjusting for body mass index.
• Smoking was found to significantly increase visceral fat accumulation.
• No mediating role was observed for cortisol or sex hormones.

Conclusions:

• Smoking initiation and higher lifetime smoking levels causally contribute to increased abdominal fat distribution.
• The increase in abdominal fat associated with smoking is primarily characterized by visceral fat.
• Smoking cessation efforts may lead to a reduction in abdominal fat, offering additional public health benefits.