The causal association between circulating zinc, magnesium, and other minerals with autism spectrum disorder: a Mendelian randomization study

Bing-Quan ZHU, Sai-Jing CHEN, Tian-Miao GU, Si-Run JIN, Dan YAO, Shuang-Shuang ZHENG, Jie SHAO

Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (9) : 1098-1104.

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Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (9) : 1098-1104. DOI: 10.7499/j.issn.1008-8830.2506025
CLINICAL RESEARCH

The causal association between circulating zinc, magnesium, and other minerals with autism spectrum disorder: a Mendelian randomization study

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Abstract

Objective To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). Methods A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. Results No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. Conclusions This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.

Key words

Autism spectrum disorder / Zinc / Magnesium / Mendelian randomization / Causal association / Child

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Bing-Quan ZHU , Sai-Jing CHEN , Tian-Miao GU , et al . The causal association between circulating zinc, magnesium, and other minerals with autism spectrum disorder: a Mendelian randomization study[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(9): 1098-1104 https://doi.org/10.7499/j.issn.1008-8830.2506025

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