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Paul Franks

Paul Franks

Principal investigator

Paul Franks

Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations

Author

  • 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 M.W. 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

Summary, in English

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.

Department/s

  • Genetic and Molecular Epidemiology
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Internal Medicine - Epidemiology

Publishing year

2021

Language

English

Pages

98-106

Publication/Series

Diabetes Care

Volume

44

Issue

1

Document type

Journal article

Publisher

American Diabetes Association

Topic

  • Endocrinology and Diabetes
  • Medical Genetics

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 0149-5992