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Background <p>Gliomas, particularly glioblastoma multiforme (GBM), are among the most aggressive brain tumors with poor prognoses. Previous studies have suggested potential links between dietary factors and glioma risk, but the evidence remains inconsistent.</p> Methods <p>We conducted a bidirectional two-sample Mendelian Randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) of 4 macronutrients (protein, carbohydrate, sugar and fat), 14 micronutrients (vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, carotene, folate, zinc, calcium, iron, magnesium, copper, potassium, and selenium), and glioma risk, including both GBM and non-GBM subtypes. The inverse-variance weighted (IVW) method was used as the primary analysis, supplemented by sensitivity analyses to assess pleiotropy and heterogeneity.</p> Results <p>In forward MR analysis, genetically predicted levels of iron were linked to a decreased risk of developing GBM (odds ratio (OR): 0.5359, 95% confidence interval (CI): 0.3030–0.9475; <i>P</i> = 0.032). Additionally, vitamin D was linked to a higher likelihood of both glioma (OR: 1.6633, 95% CI: 1.0502–2.6343, <i>P</i> = 0.030) and GBM (OR: 1.7995, 95% CI: 1.0227–3.1663, <i>P</i> = 0.042). Furthermore, carbohydrate intake was positively associated with GBM risk (OR: 1.6763, 95% CI: 1.0381–2.7069, <i>P</i> = 0.035). No substantial causal relationships were found for the remaining nutrients, and reverse MR analyses detected no evidence of glioma affecting nutrient levels.</p> Conclusion <p>Our findings implicate specific nutrients, such as carbohydrate, vitamin D, and iron, in influencing glioma risk. Future studies should further explore the underlying mechanisms and validate these findings in larger, more diverse cohorts.</p>

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Macronutrients and micronutrients in relation to glioma: a bidirectional two-sample mendelian randomization analysis

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Jing Sun,
  • Xiaoshan Ma,
  • Nan Wang,
  • Xige Yang,
  • Yubo Wang

摘要

Background

Gliomas, particularly glioblastoma multiforme (GBM), are among the most aggressive brain tumors with poor prognoses. Previous studies have suggested potential links between dietary factors and glioma risk, but the evidence remains inconsistent.

Methods

We conducted a bidirectional two-sample Mendelian Randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) of 4 macronutrients (protein, carbohydrate, sugar and fat), 14 micronutrients (vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, carotene, folate, zinc, calcium, iron, magnesium, copper, potassium, and selenium), and glioma risk, including both GBM and non-GBM subtypes. The inverse-variance weighted (IVW) method was used as the primary analysis, supplemented by sensitivity analyses to assess pleiotropy and heterogeneity.

Results

In forward MR analysis, genetically predicted levels of iron were linked to a decreased risk of developing GBM (odds ratio (OR): 0.5359, 95% confidence interval (CI): 0.3030–0.9475; P = 0.032). Additionally, vitamin D was linked to a higher likelihood of both glioma (OR: 1.6633, 95% CI: 1.0502–2.6343, P = 0.030) and GBM (OR: 1.7995, 95% CI: 1.0227–3.1663, P = 0.042). Furthermore, carbohydrate intake was positively associated with GBM risk (OR: 1.6763, 95% CI: 1.0381–2.7069, P = 0.035). No substantial causal relationships were found for the remaining nutrients, and reverse MR analyses detected no evidence of glioma affecting nutrient levels.

Conclusion

Our findings implicate specific nutrients, such as carbohydrate, vitamin D, and iron, in influencing glioma risk. Future studies should further explore the underlying mechanisms and validate these findings in larger, more diverse cohorts.