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

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  • Ju-Sheng Zheng, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Storbritannien
  • Jian'an Luan, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Eleni Sofianopoulou, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Storbritannien
  • Fumiaki Imamura, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Isobel D Stewart, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Felix R Day, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Maik Pietzner, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Eleanor Wheeler, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Luca A Lotta, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Thomas E Gundersen, Vitas Ltd, Oslo, Norge
  • Pilar Amiano, Biodonostia Health Research Institute, Spanien
  • Eva Ardanaz, Navarra Public Health Institute, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spanien
  • María-Dolores Chirlaque, IMIB-Arrixaca, Murcia University, CIBERESP, Murcia, Spain., Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spanien
  • Guy Fagherazzi, Population Health Department, Luxembourg Institute of Health, Strassen, Luxembourg., Center of Epidemiology and Population Health, UMR 1018, INSERM, Paris South - Paris Saclay University, Gustave Roussy Institute, Villejuif, Luxemborg
  • Paul W Franks, Department of Clinical Sciences, Lund University, Malmö, 22362, Sweden., Sverige
  • Rudolf Kaaks, German Cancer Research Center (DKFZ), Tyskland
  • Nasser Laouali, Center of Epidemiology and Population Health, UMR 1018, INSERM, Paris South - Paris Saclay University, Gustave Roussy Institute, Villejuif, Frankrig
  • Francesca Romana Mancini, Center of Epidemiology and Population Health, UMR 1018, INSERM, Paris South - Paris Saclay University, Gustave Roussy Institute, Villejuif, Frankrig
  • Peter M Nilsson, Department of Clinical Sciences, Lund University, Malmö, 22362, Sweden., Sverige
  • N Charlotte Onland-Moret, Julius Center for Health Sciences and Primary Care, Cancer Epidemiology University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands., Holland
  • Anja Olsen
  • Kim Overvad
  • Salvatore Panico, EPIC Centre of Naples. Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy., Italien
  • Domenico Palli, Institute for Cancer Research, Italien
  • Fulvio Ricceri, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Turin, Italy., Italien
  • Olov Rolandsson, University of Umeå, Umeå, Sweden., Sverige
  • Annemieke M W Spijkerman, National Institute for Public Health and the Environment (RIVM), Bilthoven, Holland
  • María-José Sánchez, Andalusian School of Public Health, Granada, Spain., Spanien
  • Matthias B Schulze, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany., German Center for Diabetes Research (DZD), München-Neuherberg, Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany., Tyskland
  • Núria Sala, Bellvitge Biomedical Research Institute (IDIBELL), Department of Pathology, Bellvitge University Hospital, L'Hospitalet, Barcelona, 08908 Catalonia, Spain., Spanien
  • Sabina Sieri, Epidemiology and Prevention Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano Via Venezian, Milan, Italien
  • Anne Tjønneland, Department of Public Health; Aarhus University, Denmark., Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen , Danmark
  • Rosario Tumino, Cancer Registry and Histopathology Department, Azienda Sanitaria Provinciale (ASP) Ragusa, Italy., Italien
  • Yvonne T van der Schouw, Julius Center for Health Sciences and Primary Care, Cancer Epidemiology University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands., Holland
  • Elisabete Weiderpass, International Agency for Research on Cancer Lyon, France., Frankrig
  • Elio Riboli, Imperial Coll London, Imperial College London, Imperial Clin Trials Unit, Storbritannien
  • John Danesh, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Trinity Ln, Cambridge CB2 1TN, UK., British Heart Foundation Center of Research Excellence, University of Cambridge, Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK., National Institute for Health Research Cambridge Biomedical Research Center, University of Cambridge and Cambridge University Hospitals, Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Storbritannien
  • Adam S Butterworth, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Center, University of Cambridge and Cambridge University Hospitals, Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK., Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Storbritannien
  • Stephen J Sharp, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Claudia Langenberg, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Nita G Forouhi, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien
  • Nicholas J Wareham, Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K., Storbritannien

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.

OriginalsprogEngelsk
Artikelnummerdc20-1328
TidsskriftDiabetes Care
Vol/bind44
Nummer1
Sider (fra-til)98-106
Antal sider9
ISSN0149-5992
DOI
StatusUdgivet - jan. 2021

Bibliografisk note

© 2020 by the American Diabetes Association.

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