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, Maria-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, Maria-Jose Sanchez, Matthias Bernd Schulze, Nuria Sala, Sabina Sieri, Anne Tjonneland, 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
- 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 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF,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 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).
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.…
MetadatenAuthor details: | Ju-Sheng ZhengORCiD, Jian'an Luan, Eleni Sofianopoulou, Fumiaki Imamura, Isobel D. Stewart, Felix R. Day, Maik PietznerORCiD, Eleanor Wheeler, Luca A. LottaORCiD, Thomas E. Gundersen, Pilar Amiano, Eva Ardanaz, Maria-Dolores Chirlaque, Guy FagherazziORCiD, Paul W. FranksORCiD, Rudolf Kaaks, Nasser Laouali, Francesca Romana Mancini, Peter M. Nilsson, N. Charlotte Onland-Moret, Anja Olsen, Kim OvervadORCiD, Salvatore Panico, Domenico Palli, Fulvio Ricceri, Olov RolandssonORCiD, Annemieke M. W. Spijkerman, Maria-Jose Sanchez, Matthias Bernd SchulzeORCiDGND, Nuria Sala, Sabina Sieri, Anne TjonnelandORCiD, Rosario Tumino, Yvonne T. van der Schouw, Elisabete Weiderpass, Elio RiboliORCiD, John Danesh, Adam S. Butterworth, Stephen J. Sharp, Claudia Langenberg, Nita G. ForouhiORCiD, Nicholas J. WarehamORCiD |
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DOI: | https://doi.org/10.2337/dc20-1328 |
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ISSN: | 0149-5992 |
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ISSN: | 1935-5548 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33203707 |
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Title of parent work (English): | Diabetes care |
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Subtitle (English): | genome-wide association study and Mendelian randomization analysis in European populations |
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Publisher: | American Diabetes Association |
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Place of publishing: | Alexandria |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2020/11/17 |
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Publication year: | 2020 |
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Release date: | 2022/11/04 |
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Volume: | 44 |
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Issue: | 1 |
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Number of pages: | 9 |
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First page: | 98 |
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Last Page: | 106 |
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Funding institution: | European Union Sixth Framework ProgrammeEuropean Commission [LSHM_CT_2006_037197]; Medical Research Council Epidemiology UnitUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_UU_ 12015/1, MC_UU_12015/5]; National Institute for Health Research Biomedical Research Center Cambridge [IS-BRC-1215-20014]; European Commission (DG-SANCO)European CommissionEuropean Commission Joint Research Centre; International Agency for Research on Cancer; Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII); Regional Government of AndaluciaJunta de Andalucia; Regional Government of AsturiasPrincipality of Asturias; Regional Government of Basque CountryBasque Government; Regional Government of Murcia; Regional Government of Navarra; Catalan Institute of Oncology - ICO (Spain); Medical Research Council Cambridge InitiativeUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [RG71466, SJAH/004]; EPIC-CVD project - European Union Framework 7 [HEALTH-F2-2012-279233]; European Research CouncilEuropean Research Council (ERC)European Commission [268834]; UK Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0800270, MR/L003120/1]; British Heart FoundationBritish Heart Foundation [SP/09/002, RG/08/014, RG13/13/30194]; UK National Institute for Health Research (Cambridge Biomedical Research Center at the Cambridge University Hospitals National Health Service Foundation Trust); Health Data Research UK - UK Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Engineering and Physical Sciences Research CouncilUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC); Economic and Social Research CouncilUK Research & Innovation (UKRI)Economic & Social Research Council (ESRC); Department of Health and Social Care (England); Chief Scientist Office of the Scottish Government Health; Social Care Directorates; Health and Social Care Research and Development Division (Welsh Government); Public Health Agency (Northern Ireland); British Heart FoundationBritish Heart Foundation; Wellcome; European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Actions grant [701708]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81903316]; Zhejiang Ten-thousand Talents Program [2019R52039]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_UU_00006/3, MC_UU_12015/5, MC_UU_12015/1, MC_UU_00006/1] Funding Source: UKRI |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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