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000165959 1001_ $$00000-0001-6560-4890$$aZheng, Ju-Sheng$$b0
000165959 245__ $$aPlasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.
000165959 260__ $$aAlexandria, Va.$$bAssoc.$$c2021
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000165959 500__ $$a2021 Jan;44(1):98-106
000165959 520__ $$aHigher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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000165959 7001_ $$aLuan, Jian'an$$b1
000165959 7001_ $$aSofianopoulou, Eleni$$b2
000165959 7001_ $$aImamura, Fumiaki$$b3
000165959 7001_ $$aStewart, Isobel D$$b4
000165959 7001_ $$aDay, Felix R$$b5
000165959 7001_ $$aPietzner, Maik$$b6
000165959 7001_ $$aWheeler, Eleanor$$b7
000165959 7001_ $$00000-0002-2619-5956$$aLotta, Luca A$$b8
000165959 7001_ $$aGundersen, Thomas E$$b9
000165959 7001_ $$aAmiano, Pilar$$b10
000165959 7001_ $$aArdanaz, Eva$$b11
000165959 7001_ $$aChirlaque, María-Dolores$$b12
000165959 7001_ $$00000-0001-5033-5966$$aFagherazzi, Guy$$b13
000165959 7001_ $$00000-0002-0520-7604$$aFranks, Paul W$$b14
000165959 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b15$$udkfz
000165959 7001_ $$aLaouali, Nasser$$b16
000165959 7001_ $$aMancini, Francesca Romana$$b17
000165959 7001_ $$aNilsson, Peter M$$b18
000165959 7001_ $$aOnland-Moret, N Charlotte$$b19
000165959 7001_ $$aOlsen, Anja$$b20
000165959 7001_ $$aOvervad, Kim$$b21
000165959 7001_ $$aPanico, Salvatore$$b22
000165959 7001_ $$aPalli, Domenico$$b23
000165959 7001_ $$aRicceri, Fulvio$$b24
000165959 7001_ $$00000-0002-1341-6828$$aRolandsson, Olov$$b25
000165959 7001_ $$aSpijkerman, Annemieke M W$$b26
000165959 7001_ $$aSánchez, María-José$$b27
000165959 7001_ $$00000-0002-0830-5277$$aSchulze, Matthias B$$b28
000165959 7001_ $$aSala, Núria$$b29
000165959 7001_ $$aSieri, Sabina$$b30
000165959 7001_ $$aTjønneland, Anne$$b31
000165959 7001_ $$aTumino, Rosario$$b32
000165959 7001_ $$avan der Schouw, Yvonne T$$b33
000165959 7001_ $$aWeiderpass, Elisabete$$b34
000165959 7001_ $$aRiboli, Elio$$b35
000165959 7001_ $$aDanesh, John$$b36
000165959 7001_ $$aButterworth, Adam S$$b37
000165959 7001_ $$aSharp, Stephen J$$b38
000165959 7001_ $$aLangenberg, Claudia$$b39
000165959 7001_ $$00000-0002-5041-248X$$aForouhi, Nita G$$b40
000165959 7001_ $$00000-0003-1422-2993$$aWareham, Nicholas J$$b41
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