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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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
  • Maria-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
  • Maria-Jose Sanchez
  • Matthias B. Schulze
  • Nuria Sala
  • Sabina Sieri
  • 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

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.

OriginalsprogEngelsk
TidsskriftDiabetes Care. Supplement
Vol/bind44
Udgave nummer1
Sider (fra-til)98-106
Antal sider9
ISSN0149-5992
DOI
StatusUdgivet - jan. 2021

ID: 254516321