| Title: | Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations |
| Journal: | Diabetes Care |
| Published: | 17 Nov 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33203707/ |
| DOI: | https://doi.org/10.2337/dc20-1328 |
| URL: | https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf |
Publication 13703
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Abstract
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.</p>
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.</p>
RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 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).</p>
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.</p>
8 Keywords
- Ascorbic Acid
- Delta-5 Fatty Acid Desaturase
- Diabetes Mellitus, Type 2
- Genome-Wide Association Study
- Humans
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Risk Factors
42 Authors
- Ju-Sheng Zheng
- Jian'an Luan
- Eleni Sofianopoulou
- Fumiaki Imamura
- Isobel D. Stewart
- Felix R. Day
- Maik Pietzner
- Eleanor Wheeler
- Luca A. Lotta
- Thomas E. Gundersen
- Pilar Amiano
- Eva Ardanaz
- María-Dolores Chirlaque
- Guy Fagherazzi
- Paul W. Franks
- Rudolf Kaaks
- Nasser Laouali
- Francesca Romana Mancini
- Peter M. Nilsson
- N. Charlotte Onland-Moret
- Anja Olsen
- Kim Overvad
- Salvatore Panico
- Domenico Palli
- Fulvio Ricceri
- Olov Rolandsson
- Annemieke M.W. Spijkerman
- María-José Sánchez
- Matthias B. Schulze
- Núria Sala
- Sabina Sieri
- Anne Tjønneland
- Rosario Tumino
- Yvonne T. van der Schouw
- Elisabete Weiderpass
- Elio Riboli
- John Danesh
- Adam S. Butterworth
- Stephen J. Sharp
- Claudia Langenberg
- Nita G. Forouhi
- Nicholas J. Wareham
1 Application
| Application ID | Title |
|---|---|
| 44448 | The genetic and environmental determinants of cardiometabolic and related disorders. |
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