Obesity and peripheral arterial disease: A Mendelian Randomization analysis

Area of Science:

• Cardiovascular Epidemiology
• Genetic Epidemiology
• Metabolic Disease Research

Background:

• Observational studies identify obesity as a significant risk factor for peripheral arterial disease (PAD).
• Conventional epidemiological methods are limited by potential residual confounding factors.
• Mendelian Randomization (MR) offers a robust approach to investigate causal relationships, minimizing bias.

Purpose of the Study:

• To ascertain the causal role of obesity in the development of peripheral arterial disease (PAD).
• To utilize a Mendelian Randomization (MR) approach to overcome limitations of observational studies.
• To provide stronger evidence for the etiological link between body mass and PAD.

Main Methods:

• A Mendelian Randomization (MR) analysis was conducted on 11,477 adults aged 40+ in Shanghai.
• Genotyping of 14 validated body mass index (BMI)-associated common variants in East Asians.
• Peripheral arterial disease (PAD) defined by ankle-to-brachial index (ABI) <0.90 or >1.40; weighted BMI genetic risk score (GRS) used as instrumental variable.

Main Results:

• Increased BMI-GRS showed a significant association with higher BMI (0.43 kg/m(2) per SD increase).
• Higher BMI-GRS significantly increased the odds of PAD (OR 1.17 per SD increase).
• MR analysis demonstrated a causal effect of obesity on PAD (OR 1.44 per BMI unit).

Conclusions:

• Obesity is suggested to be causally associated with peripheral arterial disease (PAD).
• The causal link persists after adjusting for potential intermediate factors like hypertension, dyslipidemia, and hyperglycemia.
• This MR study strengthens the evidence for obesity as an etiological factor in PAD development.