Article Text
Abstract
Background Circulating antioxidants are associated with a lower risk of Alzheimer’s disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR).
Methods Single nucleotide polymorphisms strongly (p<5×10−8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, β-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis.
Results Higher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (β=−0.026, 95% CI −0.044 to −0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses.
Conclusion Our results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.
- AGING
- COGNITION
- DEMENTIA
- MENDELIAN RANDOMIZATION ANALYSIS
- NUTRITION
Data availability statement
Data are available in a public, open access repository. The data sets for MR analysis of this article are available from published genome-wide association studies: https://doi.org/10.1093/hmg/ddr387, https://doi.org/10.2337/dc20-1328, https://doi.org/10.1093/hmg/ddt239, https://doi.org/10.1093/hmg/ddu546, https://doi.org/10.1016/j.ajhg.2008.12.019, https://doi.org/10.1038/ng.2500, https://doi.org/10.1038/s41588-020-00776-w, https://doi.org/10.1038/s41588-018-0147-3, https://doi.org/10.1038/s41467-018-04362-x, https://www.nature.com/articles/s41588-018-0311-9.
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Data availability statement
Data are available in a public, open access repository. The data sets for MR analysis of this article are available from published genome-wide association studies: https://doi.org/10.1093/hmg/ddr387, https://doi.org/10.2337/dc20-1328, https://doi.org/10.1093/hmg/ddt239, https://doi.org/10.1093/hmg/ddu546, https://doi.org/10.1016/j.ajhg.2008.12.019, https://doi.org/10.1038/ng.2500, https://doi.org/10.1038/s41588-020-00776-w, https://doi.org/10.1038/s41588-018-0147-3, https://doi.org/10.1038/s41467-018-04362-x, https://www.nature.com/articles/s41588-018-0311-9.
Footnotes
JW and YH are joint first authors.
Contributors JW, YYH, CB, HY, ZL and LX all have substantial contributions to the conception and design and to the interpretation of the data. JW and YYH analysed the data and drafted the article. LX, CB, HY and ZL revised it critically for important intellectual content. YYH is co-first author. LX acts as the guarantor. All authors contributed to the final approval of the paper.
Funding This work was funded by the National Natural Science Foundation of China (82373661 and 82103930) and the Natural Science Foundation of Guangdong (2022A1515011546). The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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