Plasma vitamin C and type 2 diabetes: Genome-wide association study and Mendelian randomization analysis in European populations.

  • Deep Digital Phenotyping Research Unit
November 17, 2020 By:
  • Zheng JS
  • Luan J
  • Sofianopoulou E
  • Imamura F
  • Stewart ID
  • Day FR
  • Pietzner M
  • Wheeler E
  • Lotta LA
  • Gundersen TE
  • Amiano P
  • Ardanaz E
  • Chirlaque MD
  • Fagherazzi G
  • Franks PW
  • Kaaks R
  • Laouali N
  • Mancini FR
  • Nilsson PM
  • Onland-Moret NC
  • Olsen A
  • Overvad K
  • Panico S
  • Palli D
  • Ricceri F
  • Rolandsson O
  • Spijkerman AMW
  • Sanchez MJ
  • Schulze MB
  • Sala N
  • Sieri S
  • Tjonneland A
  • Tumino R
  • van der Schouw YT
  • Weiderpass E
  • Riboli E
  • Danesh J
  • Butterworth AS
  • Sharp SJ
  • Langenberg C
  • Forouhi NG
  • Wareham NJ.

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.

2020 Nov. Diabetes Care. Online ahead of print.
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