Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis
Abstract 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 Mendelian randomization (MR) analysis. Methods Single nucle...
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Springer
2025-03-01
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| Series: | Eating and Weight Disorders |
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| Online Access: | https://doi.org/10.1007/s40519-025-01730-7 |
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| author | Rui Zhou Yanxiang Zhang Jiazhi Wang Huacong Huang Tianyou Liao Weisheng Lai Yongle Ju Manzhao Ouyang |
| author_facet | Rui Zhou Yanxiang Zhang Jiazhi Wang Huacong Huang Tianyou Liao Weisheng Lai Yongle Ju Manzhao Ouyang |
| author_sort | Rui Zhou |
| collection | DOAJ |
| description | Abstract 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 Mendelian randomization (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 odds ratio [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. |
| format | Article |
| id | doaj-art-33231ad6d35e45b89b99513209cae813 |
| institution | DOAJ |
| issn | 1590-1262 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
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| series | Eating and Weight Disorders |
| spelling | doaj-art-33231ad6d35e45b89b99513209cae8132025-08-20T02:49:30ZengSpringerEating and Weight Disorders1590-12622025-03-013011810.1007/s40519-025-01730-7Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysisRui Zhou0Yanxiang Zhang1Jiazhi Wang2Huacong Huang3Tianyou Liao4Weisheng Lai5Yongle Ju6Manzhao Ouyang7Surgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversitySurgical Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical UniversityAbstract 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 Mendelian randomization (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 odds ratio [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.https://doi.org/10.1007/s40519-025-01730-7ObesityMicronutrientsMendelian randomizationRisk factorGenome-wide association study |
| spellingShingle | Rui Zhou Yanxiang Zhang Jiazhi Wang Huacong Huang Tianyou Liao Weisheng Lai Yongle Ju Manzhao Ouyang Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis Eating and Weight Disorders Obesity Micronutrients Mendelian randomization Risk factor Genome-wide association study |
| title | Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis |
| title_full | Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis |
| title_fullStr | Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis |
| title_full_unstemmed | Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis |
| title_short | Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis |
| title_sort | establishing the relationships between obesity and genetically predicted serum micronutrient levels a multivariable mendelian randomization analysis |
| topic | Obesity Micronutrients Mendelian randomization Risk factor Genome-wide association study |
| url | https://doi.org/10.1007/s40519-025-01730-7 |
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