Plasma vitamin C and type 2 diabetes: genome-wide association study and Mendelian randomization analysis in European populations
Year: 2020
Type: other
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 difference in plasma vitamin C with type 2 diabetes in up-to 80,983 cases and 842,909 non-cases. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 cases and 11,073 non-cases. 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 standard deviation, 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.
Authors: 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, María-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 MW Spijkerman, María-José Sánchez, Matthias B Schulze, Núria Sala, Sabina Sieri, Anne Tjønneland, 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
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4236413134