Dataset Information

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.

SUBMITTER: Zheng JS

PROVIDER: S-EPMC7783939 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Zheng Ju-Sheng JS Luan Jian'an J Sofianopoulou Eleni E Imamura Fumiaki F Stewart Isobel D ID Day Felix R FR Pietzner Maik M Wheeler Eleanor E Lotta Luca A LA Gundersen Thomas E TE Amiano Pilar P Ardanaz Eva E Chirlaque María-Dolores MD Fagherazzi Guy G Franks Paul W PW Kaaks Rudolf R Laouali Nasser N Mancini Francesca Romana FR Nilsson Peter M PM Onland-Moret N Charlotte NC Olsen Anja A Overvad Kim K Panico Salvatore S Palli Domenico D Ricceri Fulvio F Rolandsson Olov O Spijkerman Annemieke M W AMW Sánchez María-José MJ Schulze Matthias B MB Sala Núria N Sieri Sabina S Tjønneland Anne A Tumino Rosario R van der Schouw Yvonne T YT Weiderpass Elisabete E Riboli Elio E Danesh John J Butterworth Adam S AS Sharp Stephen J SJ Langenberg Claudia C Forouhi Nita G NG Wareham Nicholas J NJ

Diabetes care 20201117 1

<h4>Objective</h4>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.<h4>Research design and methods</h4>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 estimat ...[more]

PMID: 33203707

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Dataset Information

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

Objective

Research design and methods

Results

Conclusions

Publications

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

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