ArticleGenes & nutrition2021
Mendelian randomization to evaluate the effect of plasma vitamin C levels on the risk of Alzheimer's disease.
Article in Genes & nutrition, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Potential biases associated with reported parental history of dementia in the Alzheimer's Disease Research Center cohorts: Implications for secondary data analyses.Journal of Alzheimer's disease : JAD · 2026Article
- The Relation of Serum Vitamin C Concentrations with Alzheimer's Disease Mortality in a National Cohort of Community-Dwelling Elderly Adults.Nutrients · 2024Article
- Revisiting the Role of Vitamins and Minerals in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Diet in the Prevention of Alzheimer's Disease: Current Knowledge and Future Research Requirements.Nutrients · 2022Review
- Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX.Alzheimer's research & therapy · 2022Article
- Mendelian randomization analysis of the causal association of bone mineral density and fracture with multiple sclerosis.Frontiers in neurology · 2022Article
- Educational Attainment and Ischemic Stroke: A Mendelian Randomization Study.Frontiers in genetics · 2021Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveUntil now, observational studies have explored the impact of vitamin C intake on Alzheimer's disease (AD) risk, however, reported ambiguous findings. To develop effective therapies or prevention, the causal link between vitamin C levels and AD should be established.
methodsHere, we selected 11 plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (N = 52,018) as the potential instrumental variables. We extracted their corresponding summary statistics from large-scale IGAP clinically diagnosed AD GWAS dataset (N = 63,926) and UK Biobank AD proxy phenotype GWAS dataset (N = 314,278), as well as two UK Biobank subgroups including the maternal AD group (27,696 cases of maternal AD and 260,980 controls) and paternal AD group (14,338 cases of paternal AD and 245,941 controls). We then performed a Mendelian randomization (MR) study to evaluate the causal association between plasma vitamin C levels and the risk of AD and AD proxy phenotype. Meanwhile, we further verified these findings using a large-scale cognitive performance GWAS dataset (N = 257,841).
resultsIn IGAP, we found no significant causal association between plasma vitamin C levels and the risk of AD. In UK Biobank, we found that per 1 SD increase in plasma vitamin C levels (about 20.2 μmol/l) was significantly associated with the reduced risk of AD proxy phenotype (OR = 0.93, 95% CI 0.88-0.98, P = 7.00E-03). A subgroup MR analysis in UK Biobank indicated that per 1 SD increase in plasma vitamin C levels could significantly reduce the risk of AD proxy phenotype in the maternal AD group (OR = 0.89, 95% CI 0.84-0.94, P = 7.29E-05), but not in the paternal AD group (OR = 1.02, 95% CI 0.92-1.12, P = 7.59E-01). The leave-one-out permutation further showed that the SLC23A1 rs33972313 variant largely changed the precision of the overall MR estimates in all these four GWAS datasets. Meanwhile, we did not observe any significant causal effect of plasma vitamin C levels on the cognitive performance.
conclusionWe demonstrated that there may be no causal association between plasma vitamin C levels and the risk of AD in people of European descent. The insistent findings in clinically diagnosed AD and AD proxy phenotype may be caused by the phenotypic heterogeneity.
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