The causal association between body composition and 25-hydroxyvitamin D levels: A bidirectional Mendelian...

Area of Science:

• Genetics and Epidemiology
• Nutritional Science
• Metabolic Health

Background:

• Observational studies suggest a link between obesity and vitamin D deficiency.
• The causal direction of this relationship remains unclear.
• Mendelian randomization offers a robust method to investigate causality.

Purpose of the Study:

• To investigate the bidirectional causal relationship between obesity-associated metrics and 25-hydroxyvitamin D (25(OH)D) levels.
• To determine if obesity metrics influence vitamin D levels or vice versa.
• To provide robust evidence on the etiological link between obesity and vitamin D status.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis was performed.
• Instrumental variables for body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BFP), and whole body fat mass (WFM) were selected.
• Inverse variance weighted (IVW), MR Egger, and weighted median methods were employed.
• Sensitivity analyses using MR-PRESSO assessed heterogeneity and pleiotropy.

Main Results:

• Statistically significant causal associations were found between higher BMI, WHR, BFP, and WFM and decreased 25(OH)D levels (all P < .001).
• No significant causal effect of 25(OH)D levels on the obesity-related body metrics was observed.
• Sensitivity analyses confirmed the robustness of the findings, with no substantial heterogeneity or pleiotropy detected.

Conclusions:

• This study provides strong evidence for a causal effect of obesity-related body components on reduced 25(OH)D levels.
• The findings exclude a significant reverse causal relationship, indicating obesity influences vitamin D status.
• These results have implications for understanding the interplay between metabolic health and vitamin D in public health.