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

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@article{063a1e11fbd644ef9d99c85911fd65c0,
title = "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.",
author = "Zheng, {Ju Sheng} and Jian{\textquoteright}An Luan and Eleni Sofianopoulou and Fumiaki Imamura and Stewart, {Isobel D.} and Day, {Felix R.} and Maik Pietzner and Eleanor Wheeler and Lotta, {Luca A.} and Gundersen, {Thomas E.} and Pilar Amiano and Eva Ardanaz and Chirlaque, {Mar{\'i}a Dolores} and Guy Fagherazzi and Franks, {Paul W.} and Rudolf Kaaks and Nasser Laouali and Mancini, {Francesca Romana} and Nilsson, {Peter M.} and {Charlotte Onland-Moret}, N. and Anja Olsen and Kim Overvad and Salvatore Panico and Domenico Palli and Fulvio Ricceri and Olov Rolandsson and Spijkerman, {Annemieke M.W.} and S{\'a}nchez, {Mar{\'i}a Jos{\'e}} and Schulze, {Matthias B.} and N{\'u}ria Sala and Sabina Sieri and Anne Tj{\o}nneland and Rosario Tumino and {van der Schouw}, {Yvonne T.} and Elisabete Weiderpass and Elio Riboli and John Danesh and Butterworth, {Adam S.} and Sharp, {Stephen J.} and Claudia Langenberg and Forouhi, {Nita G.} and Wareham, {Nicholas J.}",
year = "2021",
doi = "10.2337/dc20-1328",
language = "English",
volume = "44",
pages = "98--106",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association",
number = "1",

}