TY  - JOUR
A1  - Zheng, Ju-Sheng
A1  - Luan, Jian'an
A1  - Sofianopoulou, Eleni
A1  - Imamura, Fumiaki
A1  - Stewart, Isobel D.
A1  - Day, Felix R.
A1  - Pietzner, Maik
A1  - Wheeler, Eleanor
A1  - Lotta, Luca A.
A1  - Gundersen, Thomas E.
A1  - Amiano, Pilar
A1  - Ardanaz, Eva
A1  - Chirlaque, Maria-Dolores
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Kaaks, Rudolf
A1  - Laouali, Nasser
A1  - Mancini, Francesca Romana
A1  - Nilsson, Peter M.
A1  - Onland-Moret, N. Charlotte
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Panico, Salvatore
A1  - Palli, Domenico
A1  - Ricceri, Fulvio
A1  - Rolandsson, Olov
A1  - Spijkerman, Annemieke M. W.
A1  - Sanchez, Maria-Jose
A1  - Schulze, Matthias B.
A1  - Sala, Nuria
A1  - Sieri, Sabina
A1  - Tjonneland, Anne
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Weiderpass, Elisabete
A1  - Riboli, Elio
A1  - Danesh, John
A1  - Butterworth, Adam S.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Forouhi, Nita G.
A1  - Wareham, Nicholas J.
T1  - Plasma vitamin C and type 2 diabetes
BT  - genome-wide association study and Mendelian randomization analysis in European populations
JF  - Diabetes care
N2  - 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.
Y1  - 2020
U6  - https://doi.org/10.2337/dc20-1328
SN  - 0149-5992
SN  - 1935-5548
VL  - 44
IS  - 1
SP  - 98
EP  - 106
PB  - American Diabetes Association
CY  - Alexandria
ER  -