Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations

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Plasma Vitamin C and Type 2 Diabetes : Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations. / Zheng, Ju-Sheng; Luan, Jian'an; Sofianopoulou, Eleni; Imamura, Fumiaki; Stewart, Isobel D.; Day, Felix R.; Pietzner, Maik; Wheeler, Eleanor; Lotta, Luca A.; Gundersen, Thomas E.; Amiano, Pilar; Ardanaz, Eva; Chirlaque, Maria-Dolores; Fagherazzi, Guy; Franks, Paul W.; Kaaks, Rudolf; Laouali, Nasser; Mancini, Francesca Romana; Nilsson, Peter M.; Onland-Moret, N. Charlotte; Olsen, Anja; Overvad, Kim; Panico, Salvatore; Palli, Domenico; Ricceri, Fulvio; Rolandsson, Olov; Spijkerman, Annemieke M. W.; Sanchez, Maria-Jose; Schulze, Matthias B.; Sala, Nuria; Sieri, Sabina; Tjonneland, Anne; Tumino, Rosario; van der Schouw, Yvonne T.; Weiderpass, Elisabete; Riboli, Elio; Danesh, John; Butterworth, Adam S.; Sharp, Stephen J.; Langenberg, Claudia; Forouhi, Nita G.; Wareham, Nicholas J.

In: Diabetes Care. Supplement, Vol. 44, No. 1, 01.2021, p. 98-106.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zheng, J-S, Luan, J, Sofianopoulou, E, Imamura, F, Stewart, ID, Day, FR, Pietzner, M, Wheeler, E, Lotta, LA, Gundersen, TE, Amiano, P, Ardanaz, E, Chirlaque, M-D, Fagherazzi, G, Franks, PW, Kaaks, R, Laouali, N, Mancini, FR, Nilsson, PM, Onland-Moret, NC, Olsen, A, Overvad, K, Panico, S, Palli, D, Ricceri, F, Rolandsson, O, Spijkerman, AMW, Sanchez, M-J, Schulze, MB, Sala, N, Sieri, S, Tjonneland, A, Tumino, R, van der Schouw, YT, Weiderpass, E, Riboli, E, Danesh, J, Butterworth, AS, Sharp, SJ, Langenberg, C, Forouhi, NG & Wareham, NJ 2021, 'Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations', Diabetes Care. Supplement, vol. 44, no. 1, pp. 98-106. https://doi.org/10.2337/dc20-1328

APA

Zheng, J-S., Luan, J., Sofianopoulou, E., Imamura, F., Stewart, I. D., Day, F. R., Pietzner, M., Wheeler, E., Lotta, L. A., Gundersen, T. E., Amiano, P., Ardanaz, E., Chirlaque, M-D., Fagherazzi, G., Franks, P. W., Kaaks, R., Laouali, N., Mancini, F. R., Nilsson, P. M., ... Wareham, N. J. (2021). Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations. Diabetes Care. Supplement, 44(1), 98-106. https://doi.org/10.2337/dc20-1328

Vancouver

Zheng J-S, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR et al. Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations. Diabetes Care. Supplement. 2021 Jan;44(1):98-106. https://doi.org/10.2337/dc20-1328

Author

Zheng, Ju-Sheng ; Luan, Jian'an ; Sofianopoulou, Eleni ; Imamura, Fumiaki ; Stewart, Isobel D. ; Day, Felix R. ; Pietzner, Maik ; Wheeler, Eleanor ; Lotta, Luca A. ; Gundersen, Thomas E. ; Amiano, Pilar ; Ardanaz, Eva ; Chirlaque, Maria-Dolores ; Fagherazzi, Guy ; Franks, Paul W. ; Kaaks, Rudolf ; Laouali, Nasser ; Mancini, Francesca Romana ; Nilsson, Peter M. ; Onland-Moret, N. Charlotte ; Olsen, Anja ; Overvad, Kim ; Panico, Salvatore ; Palli, Domenico ; Ricceri, Fulvio ; Rolandsson, Olov ; Spijkerman, Annemieke M. W. ; Sanchez, Maria-Jose ; Schulze, Matthias B. ; Sala, Nuria ; Sieri, Sabina ; Tjonneland, Anne ; Tumino, Rosario ; van der Schouw, Yvonne T. ; Weiderpass, Elisabete ; Riboli, Elio ; Danesh, John ; Butterworth, Adam S. ; Sharp, Stephen J. ; Langenberg, Claudia ; Forouhi, Nita G. ; Wareham, Nicholas J. / Plasma Vitamin C and Type 2 Diabetes : Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations. In: Diabetes Care. Supplement. 2021 ; Vol. 44, No. 1. pp. 98-106.

Bibtex

@article{ee51f11baa8741fc96f6a5b3a7f636f0,
title = "Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations",
abstract = "OBJECTIVEHigher 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 METHODSWe 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.RESULTSWe 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).CONCLUSIONSThese 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.",
keywords = "GENETIC-VARIATION, ASCORBIC-ACID, OXIDATIVE STRESS, VEGETABLE INTAKE, EPIC-NORFOLK, LIFE-STYLE, METAANALYSIS, FRUIT, DESIGN, LEVEL",
author = "Ju-Sheng Zheng and Jian'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 Maria-Dolores Chirlaque and Guy Fagherazzi and Franks, {Paul W.} and Rudolf Kaaks and Nasser Laouali and Mancini, {Francesca Romana} and Nilsson, {Peter M.} and Onland-Moret, {N. Charlotte} and Anja Olsen and Kim Overvad and Salvatore Panico and Domenico Palli and Fulvio Ricceri and Olov Rolandsson and Spijkerman, {Annemieke M. W.} and Maria-Jose Sanchez and Schulze, {Matthias B.} and Nuria Sala and Sabina Sieri and Anne Tjonneland 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",
month = jan,
doi = "10.2337/dc20-1328",
language = "English",
volume = "44",
pages = "98--106",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association",
number = "1",

}

RIS

TY - JOUR

T1 - Plasma Vitamin C and Type 2 Diabetes

T2 - Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations

AU - Zheng, Ju-Sheng

AU - Luan, Jian'an

AU - Sofianopoulou, Eleni

AU - Imamura, Fumiaki

AU - Stewart, Isobel D.

AU - Day, Felix R.

AU - Pietzner, Maik

AU - Wheeler, Eleanor

AU - Lotta, Luca A.

AU - Gundersen, Thomas E.

AU - Amiano, Pilar

AU - Ardanaz, Eva

AU - Chirlaque, Maria-Dolores

AU - Fagherazzi, Guy

AU - Franks, Paul W.

AU - Kaaks, Rudolf

AU - Laouali, Nasser

AU - Mancini, Francesca Romana

AU - Nilsson, Peter M.

AU - Onland-Moret, N. Charlotte

AU - Olsen, Anja

AU - Overvad, Kim

AU - Panico, Salvatore

AU - Palli, Domenico

AU - Ricceri, Fulvio

AU - Rolandsson, Olov

AU - Spijkerman, Annemieke M. W.

AU - Sanchez, Maria-Jose

AU - Schulze, Matthias B.

AU - Sala, Nuria

AU - Sieri, Sabina

AU - Tjonneland, Anne

AU - Tumino, Rosario

AU - van der Schouw, Yvonne T.

AU - Weiderpass, Elisabete

AU - Riboli, Elio

AU - Danesh, John

AU - Butterworth, Adam S.

AU - Sharp, Stephen J.

AU - Langenberg, Claudia

AU - Forouhi, Nita G.

AU - Wareham, Nicholas J.

PY - 2021/1

Y1 - 2021/1

N2 - OBJECTIVEHigher 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 METHODSWe 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.RESULTSWe 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).CONCLUSIONSThese 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.

AB - OBJECTIVEHigher 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 METHODSWe 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.RESULTSWe 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).CONCLUSIONSThese 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.

KW - GENETIC-VARIATION

KW - ASCORBIC-ACID

KW - OXIDATIVE STRESS

KW - VEGETABLE INTAKE

KW - EPIC-NORFOLK

KW - LIFE-STYLE

KW - METAANALYSIS

KW - FRUIT

KW - DESIGN

KW - LEVEL

U2 - 10.2337/dc20-1328

DO - 10.2337/dc20-1328

M3 - Journal article

C2 - 33203707

VL - 44

SP - 98

EP - 106

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -

ID: 254516321