Zheng, Ju-ShengLuan, Jian'anSofianopoulou, EleniImamura, FumiakiStewart, Isobel DDay, Felix RPietzner, MaikWheeler, EleanorLotta, Luca AGundersen, Thomas EAmiano, PilarArdanaz, EvaChirlaque, María-DoloresFagherazzi, GuyFranks, Paul WKaaks, RudolfLaouali, NasserMancini, Francesca RomanaNilsson, Peter MOnland-Moret, N CharlotteOlsen, AnjaOvervad, KimPanico, SalvatorePalli, DomenicoRicceri, FulvioRolandsson, OlovSpijkerman, Annemieke M WSanchez-Perez, Maria-JoseSchulze, Matthias BSala, NúriaSieri, SabinaTjønneland, AnneTumino, Rosariovan der Schouw, Yvonne TWeiderpass, ElisabeteRiboli, ElioDanesh, JohnButterworth, Adam SSharp, Stephen JLangenberg, ClaudiaForouhi, Nita GWareham, Nicholas J2023-02-092023-02-092020-11-17http://hdl.handle.net/10668/16625Higher 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. 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. We identified 11 genomic regions associated with plasma vitamin C (P 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.enAscorbic AcidDelta-5 Fatty Acid DesaturaseDiabetes Mellitus, Type 2Genome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk Factorsresearch article33203707open access10.2337/dc20-13281935-5548PMC7783939https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939/pdf