Iron status and obesity-related traits: A two-sample bidirectional Mendelian randomization study

Area of Science:

• Human Genetics
• Metabolic Disorders
• Nutritional Biochemistry

Background:

• Observational studies suggest a link between iron status and obesity, but causality remains unclear.
• Investigating causal relationships is crucial for understanding metabolic health and developing targeted interventions.

Purpose of the Study:

• To determine the causal effect of iron status on obesity-related traits (BMI, WHR) and vice versa.
• To utilize a robust Mendelian randomization approach for reliable causal inference.

Main Methods:

• Two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from European individuals.
• Employed various MR methods (IVW, MR-Egger, weighted median) and sensitivity analyses (MR-Egger intercept, Cochran's Q, leave-one-out, MR-PRESSO, RadialMR) to ensure robustness and assess pleiotropy.

Main Results:

• Genetically predicted BMI was associated with higher serum ferritin and lower serum iron and TSAT.
• No significant association was found between genetically predicted WHR and iron status.
• Genetically predicted iron status (serum ferritin, serum iron, TSAT, TIBC) did not show a causal effect on BMI or WHR.

Conclusions:

• Findings suggest that higher BMI may causally influence serum ferritin, serum iron, and TSAT levels in European populations.
• Iron status does not appear to be a causal factor for obesity traits like BMI or WHR.