Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis

Mar 29, 2025Eating and weight disorders : EWD

How Obesity Relates to Genetically Predicted Blood Levels of Vitamins and Minerals

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Abstract

Genetically predicted levels of circulating calcium and selenium are associated with an increased risk of obesity, with an of 1.478 for both.

Higher levels of circulating calcium and selenium may be causally linked to obesity risk.
The odds ratio for obesity associated with calcium is 1.625, indicating a significant relationship.
Selenium levels show an odds ratio of 1.080 for obesity risk, suggesting a potential causal influence.
No significant evidence of pleiotropy or heterogeneity was found in the analysis, implying reliable results.
Further large-scale clinical studies are needed to validate these findings.

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BACKGROUND: Previous observational studies have indicated that circulating micronutrients may influence obesity risk. This study aimed to explore the causal relationship between micronutrient levels and obesity through multivariable (MR) analysis.

METHODS: Single nucleotide polymorphisms (SNPs) significantly associated with 15 micronutrients (selenium, zinc, copper, calcium, beta-carotene, folate, iron, magnesium, potassium, and vitamins A, B6, B12, C, D, and E) from published genome-wide association studies (GWAS) were used as instrumental variables (IVs). Three obesity-related datasets were obtained from the GWAS. Inverse variance weighted (IVW) is the main method used for MR analysis. Leave-one-out analysis, MR-Pleiotropy Residual Sum and Outlier method (MR-PRESSO), weighted median, and MR-Egger method were used to assess pleiotropy and heterogeneity.

RESULTS: Genetically predicted levels of circulating selenium and calcium are causally related to the risk of obesity (calcium [OR]: 1.478, 95% confidence interval [CI] 1.128-1.935, p = 0.005; selenium OR: 1.478, 95% CI 1.128-1.935, p = 0.005). Multivariate MR analysis suggested a causal relationship between circulating selenium and calcium levels and obesity risk (calcium OR: 1.625, 95% CI 1.260-2.097; selenium OR: 1.080, 95% CI 1.003-1.163, p = 0.041). The p-value obtained in the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO were > 0.05, suggesting no significant evidence of pleiotropy or heterogeneity.

CONCLUSION: Our study revealed, for the first time, a positive correlation between elevated circulating calcium and selenium levels and an increased obesity risk. These findings provide valuable insights into obesity's underlying mechanisms. Nevertheless, further large-scale clinical studies are required to confirm our results.

LEVEL OF EVIDENCE: Level III, Mendelian randomization.

Key numbers

1.478

Increase in Obesity Risk (Calcium)

for calcium levels in relation to obesity risk.

1.478

Increase in Obesity Risk (Selenium)

for selenium levels in relation to obesity risk.

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Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis

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