Lifestyle in adulthood can modify the causal relationship between BMI and islet function: using Mendelian...

Area of Science:

• Genetics and Metabolism
• Epidemiology
• Biostatistics

Background:

• Body mass index (BMI) is closely linked to islet function, but confounding factors complicate direct causal inference.
• Mendelian randomization (MR) is a robust statistical method for identifying causal relationships by minimizing bias.
• Previous studies identified 13 East Asian BMI-related genes, necessitating further investigation into their impact on islet function.

Purpose of the Study:

• To investigate the causal relationship between East Asian BMI-related genes and islet function using Mendelian randomization.
• To assess the association between a genetic risk score derived from BMI-related genes and insulin sensitivity.
• To explore the influence of lifestyle factors (drinking, smoking) on the relationship between genetic risk score and insulin sensitivity.

Main Methods:

• A total of 2892 participants from northern China were recruited.
• Anthropometric data, lifestyle factors, fasting glucose, and insulin levels were collected; insulin sensitivity index was calculated.
• Thirteen single nucleotide polymorphisms (SNPs) in East Asian BMI-related genes were analyzed using the ABI7900HT system.

Main Results:

• Five genetic loci (CDKAL1, MAP2K5, BDNF, FTO, SEC16B) associated with BMI were used to create a genetic risk score.
• The genetic risk score showed a statistically significant negative association with the insulin sensitivity index, even after adjusting for confounders.
• Interaction analysis revealed that the negative association was absent in non-drinkers and stronger in smokers.

Conclusions:

• A negative causal relationship exists between BMI-related genetic mutations and insulin resistance.
• Acquired lifestyle factors, specifically drinking and smoking, may exacerbate this genetic predisposition to insulin resistance.