Genetically proxied vitamin B12 and homocysteine in relation to life course adiposity and body composition.

OBJECTIVE

Observational studies explore the association between vitamin B12 and obesity. However, causality is not reflected by such observations. We performed a bi-directional Mendelian randomization (MR) study to elucidate the causal relationship of vitamin B12 and homocysteine (Hcy) with life course adiposity and body composition.

METHODS

Two-sample MR analysis was conducted. Independent genetic variants associated with vitamin B12 and Hcy from large-scale genome-wide association studies (GWASs) were utilized as genetic instruments, and their causal effects on five life course adiposity phenotypes (birth weight, body mass index (BMI), childhood BMI, waist circumference, waist-to-hip ratio) and three body compositions (body fat mass, body fat-free mass, body fat percentage) were estimated from UK Biobank, other consortia, and large-scale GWASs. The inverse variance weighting (IVW, main analysis), bi-directional MR, and other six sensitivity MR analyses were performed.

RESULTS

Genetically proxied higher vitamin B12 concentrations were robustly associated with reduced BMI (Beta = -0.01, 95% confidence interval (CI) -0.016 to -0.004, P = 7.60E-04), body fat mass (Beta = -0.012, 95%CI -0.018 to -0.007, P = 1.69E-05), and body fat percentage (Beta = -0.005, 95%CI -0.009 to -0.002, P = 4.12E-03) per SD unit by IVW and other sensitivity analyses. Stratification analysis showed that these results remained significant in females and at different body sites (all P < 0.05 after Bonferroni correction). Bi-directional analyses showed no reverse causation.

CONCLUSIONS

This study provides strong evidence for the causal effect of vitamin B12 on adiposity. This gives novel clues for intervening obesity in public health and nutrition.