Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations
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OBJECTIVE
Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.
RESEARCH DESIGN AND METHODS
We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.
RESULTS
We identified 11 genomic regions associated with plasma vitamin C (P <5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).
CONCLUSIONS
These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Original language | English |
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Journal | Diabetes Care. Supplement |
Volume | 44 |
Issue number | 1 |
Pages (from-to) | 98-106 |
Number of pages | 9 |
ISSN | 0149-5992 |
DOIs | |
Publication status | Published - Jan 2021 |
- GENETIC-VARIATION, ASCORBIC-ACID, OXIDATIVE STRESS, VEGETABLE INTAKE, EPIC-NORFOLK, LIFE-STYLE, METAANALYSIS, FRUIT, DESIGN, LEVEL
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939/pdf/dc201328.pdf
Final published version
ID: 254516321