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, María Dolores; Fagherazzi, Guy; Franks, Paul W.; Kaaks, Rudolf; Laouali, Nasser; Mancini, Francesca Romana; Nilsson, Peter M.; Charlotte Onland-Moret, N.; Olsen, Anja; Overvad, Kim; Panico, Salvatore; Palli, Domenico; Ricceri, Fulvio; Rolandsson, Olov; Spijkerman, Annemieke M.W.; Sánchez, María José; Schulze, Matthias B.; Sala, Núria; Sieri, Sabina; Tjønneland, 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, Vol. 44, No. 1, 2021, p. 98-106.

Research output: Contribution to journalArticle

Harvard

Zheng, JS, Luan, JA, Sofianopoulou, E, Imamura, F, Stewart, ID, Day, FR, Pietzner, M, Wheeler, E, Lotta, LA, Gundersen, TE, Amiano, P, Ardanaz, E, Chirlaque, MD, Fagherazzi, G, Franks, PW, Kaaks, R, Laouali, N, Mancini, FR, Nilsson, PM, Charlotte Onland-Moret, N, Olsen, A, Overvad, K, Panico, S, Palli, D, Ricceri, F, Rolandsson, O, Spijkerman, AMW, Sánchez, MJ, Schulze, MB, Sala, N, Sieri, S, Tjønneland, 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, vol. 44, no. 1, pp. 98-106. https://doi.org/10.2337/dc20-1328

APA

Zheng, J. S., Luan, JA., 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, 44(1), 98-106. https://doi.org/10.2337/dc20-1328

CBE

Zheng JS, Luan JA, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Charlotte Onland-Moret N, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, Sánchez MJ, Schulze MB, Sala N, Sieri S, Tjønneland 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. 44(1):98-106. https://doi.org/10.2337/dc20-1328

MLA

Vancouver

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, María Dolores ; Fagherazzi, Guy ; Franks, Paul W. ; Kaaks, Rudolf ; Laouali, Nasser ; Mancini, Francesca Romana ; Nilsson, Peter M. ; Charlotte Onland-Moret, N. ; Olsen, Anja ; Overvad, Kim ; Panico, Salvatore ; Palli, Domenico ; Ricceri, Fulvio ; Rolandsson, Olov ; Spijkerman, Annemieke M.W. ; Sánchez, María José ; Schulze, Matthias B. ; Sala, Núria ; Sieri, Sabina ; Tjønneland, 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. 2021 ; Vol. 44, No. 1. pp. 98-106.

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, María Dolores

AU - Fagherazzi, Guy

AU - Franks, Paul W.

AU - Kaaks, Rudolf

AU - Laouali, Nasser

AU - Mancini, Francesca Romana

AU - Nilsson, Peter M.

AU - Charlotte Onland-Moret, N.

AU - Olsen, Anja

AU - Overvad, Kim

AU - Panico, Salvatore

AU - Palli, Domenico

AU - Ricceri, Fulvio

AU - Rolandsson, Olov

AU - Spijkerman, Annemieke M.W.

AU - Sánchez, María José

AU - Schulze, Matthias B.

AU - Sala, Núria

AU - Sieri, Sabina

AU - Tjønneland, 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

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.2337/dc20-1328

DO - 10.2337/dc20-1328

M3 - Article

C2 - 33203707

AN - SCOPUS:85099121347

VL - 44

SP - 98

EP - 106

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -