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

IF 2.8 3区医学 Q2 PSYCHIATRY

Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Pub Date : 2025-03-29 DOI:10.1007/s40519-025-01730-7

Rui Zhou, Yanxiang Zhang, Jiazhi Wang, Huacong Huang, Tianyou Liao, Weisheng Lai, Yongle Ju, Manzhao Ouyang

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引用次数: 0

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.

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查看原文本刊更多论文

建立肥胖和遗传预测血清微量营养素水平之间的关系：多变量孟德尔随机化分析。

背景：先前的观察性研究表明，循环微量营养素可能影响肥胖风险。本研究旨在通过多变量孟德尔随机化（MR）分析探讨微量营养素水平与肥胖之间的因果关系。方法：使用已发表的全基因组关联研究（GWAS）中与15种微量营养素（硒、锌、铜、钙、β -胡萝卜素、叶酸、铁、镁、钾和维生素A、B6、B12、C、D和E）显著相关的单核苷酸多态性（snp）作为工具变量（IVs）。从GWAS中获得三个与肥胖相关的数据集。逆方差加权（IVW）是磁共振分析的主要方法。采用留一分析、mr -多效性残差和离群值法（MR-PRESSO）、加权中位数和MR-Egger法评估多效性和异质性。结果：基因预测的循环硒和钙水平与肥胖风险有因果关系(钙比值比[OR]: 1.478, 95%可信区间[CI] 1.128-1.935, p = 0.005；OR: 1.478, 95% CI 1.128 ~ 1.935, p = 0.005)。多变量磁共振分析显示，循环硒和钙水平与肥胖风险之间存在因果关系(钙的比值比：1.625,95% CI 1.260-2.097；OR: 1.080, 95% CI 1.003-1.163, p = 0.041)。Cochrane Q检验、MR-Egger截距检验和MR-PRESSO的p值均为0.05，未发现多效性或异质性的显著证据。结论：我们的研究首次揭示了循环钙和硒水平升高与肥胖风险增加之间的正相关关系。这些发现为肥胖的潜在机制提供了有价值的见解。然而，需要进一步的大规模临床研究来证实我们的结果。证据等级：III级，孟德尔随机化。

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来源期刊

Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity 医学-精神病学

CiteScore

6.50

自引率

10.30%

发文量

170

审稿时长

>12 weeks

期刊介绍： Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity is a scientific journal whose main purpose is to create an international forum devoted to the several sectors of eating disorders and obesity and the significant relations between them. The journal publishes basic research, clinical and theoretical articles on eating disorders and weight-related problems: anorexia nervosa, bulimia nervosa, subthreshold eating disorders, obesity, atypical patterns of eating behaviour and body weight regulation in clinical and non-clinical populations.