Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

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.

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 × 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.

• 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
• Journal: Diabetes care (Diabetes Care) Vol. 44 Issue 1 Pg. 98-106 (01 2021) ISSN: 1935-5548 [Electronic] United States
• PMID: 33203707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• Delta-5 Fatty Acid Desaturase
• FADS1 protein, human
• Ascorbic Acid

Topics

• Ascorbic Acid (blood)
• Delta-5 Fatty Acid Desaturase
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• Genome-Wide Association Study
• Humans
• Mendelian Randomization Analysis
• Polymorphism, Single Nucleotide
• Risk Factors