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Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations

Zheng, Ju Sheng ; Luan, Jian’An ; Sofianopoulou, Eleni ; Imamura, Fumiaki ; Stewart, Isobel D. ; Day, Felix R. ; Pietzner, Maik ; Wheeler, Eleanor ; Lotta, Luca A. and Gundersen, Thomas E. , et al. (2021) In Diabetes Care 44(1). p.98-106
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
44
issue
1
pages
9 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85099121347
  • pmid:33203707
ISSN
0149-5992
DOI
10.2337/dc20-1328
language
English
LU publication?
yes
id
063a1e11-fbd6-44ef-9d99-c85911fd65c0
date added to LUP
2021-01-21 09:43:38
date last changed
2021-05-11 03:03:25
@article{063a1e11-fbd6-44ef-9d99-c85911fd65c0,
  abstract     = {<p>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 &lt; 5 ☓ 10<sup>-8</sup>), 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.</p>},
  author       = {Zheng, Ju Sheng and Luan, Jian’An and Sofianopoulou, Eleni and Imamura, Fumiaki and Stewart, Isobel D. and Day, Felix R. and Pietzner, Maik and Wheeler, Eleanor and Lotta, Luca A. and Gundersen, Thomas E. and Amiano, Pilar and Ardanaz, Eva and Chirlaque, María Dolores and Fagherazzi, Guy and Franks, Paul W. and Kaaks, Rudolf and Laouali, Nasser and Mancini, Francesca Romana and Nilsson, Peter M. and Charlotte Onland-Moret, N. and Olsen, Anja and Overvad, Kim and Panico, Salvatore and Palli, Domenico and Ricceri, Fulvio and Rolandsson, Olov and Spijkerman, Annemieke M.W. and Sánchez, María José and Schulze, Matthias B. and Sala, Núria and Sieri, Sabina and Tjønneland, Anne and Tumino, Rosario and van der Schouw, Yvonne T. and Weiderpass, Elisabete and Riboli, Elio and Danesh, John and Butterworth, Adam S. and Sharp, Stephen J. and Langenberg, Claudia and Forouhi, Nita G. and Wareham, Nicholas J.},
  issn         = {0149-5992},
  language     = {eng},
  number       = {1},
  pages        = {98--106},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations},
  url          = {http://dx.doi.org/10.2337/dc20-1328},
  doi          = {10.2337/dc20-1328},
  volume       = {44},
  year         = {2021},
}