The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Autor: Nita G. Forouhi, Kim Overvad, Ivonne Sluijs, Tammy Y.N. Tong, Christina C. Dahm, Kay-Tee Khaw, Thomas E. Gundersen, José María Huerta, Peter M. Nilsson, Miguel Rodríguez-Barranco, Nasser Laouali, Adam S. Butterworth, Giovanna Masala, Sara Grioni, Rosario Tumino, Anja Olsen, Stephen J. Sharp, Salvatore Panico, J. Ramón Quirós, Yvonne T. van der Schouw, Eleanor Wheeler, Rudolf Kaaks, Alicia K Heath, Eva Ardanaz, Felix R. Day, Eleni Sofianopoulou, Konstantinos K. Tsilidis, Luca A. Lotta, Nicholas J. Wareham, Douae El-Fatouhi, Claudia Langenberg, Heiner Boeing, Guy Fagherazzi, Paula Jakszyn, Olov Rolandsson, Rupal L. Shah, Mazda Jenab, Miren Dorronsoro, Ju-Sheng Zheng, Fumiaki Imamura, Isobel D. Stewart, Elio Riboli, Paul W. Franks, Louise Hansen, John Danesh, Carlotta Sacerdote, Jian'an Luan, Niki Dimou, Annemieke M.W. Spijkerman, Tilman Kühn
Přispěvatelé: Zheng, Ju-Sheng [0000-0001-6560-4890], Sharp, Stephen J [0000-0003-2375-1440], Day, Felix R [0000-0003-3789-7651], Sluijs, Ivonne [0000-0001-7758-4911], Shah, Rupal L [0000-0001-8789-8869], van der Schouw, Yvonne T [0000-0002-4605-435X], Dahm, Christina C [0000-0003-0481-2893], Dimou, Niki [0000-0003-1678-9328], Franks, Paul W [0000-0002-0520-7604], Fagherazzi, Guy [0000-0001-5033-5966], Huerta, José María [0000-0002-9637-3869], Heath, Alicia K [0000-0001-6517-1300], Hansen, Louise [0000-0002-7109-8864], Jenab, Mazda [0000-0002-0573-1852], Kühn, Tilman [0000-0001-7702-317X], Laouali, Nasser [0000-0002-8532-456X], Masala, Giovanna [0000-0002-5758-9069], Olsen, Anja [0000-0003-4788-503X], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Sacerdote, Carlotta [0000-0002-8008-5096], Tong, Tammy YN [0000-0002-0284-8959], Tumino, Rosario [0000-0003-2666-414X], Tsilidis, Konstantinos K [0000-0002-8452-8472], Riboli, Elio [0000-0001-6795-6080], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita G [0000-0002-5041-248X], Wareham, Nicholas J [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Sharp, Stephen J. [0000-0003-2375-1440], Day, Felix R. [0000-0003-3789-7651], Shah, Rupal L. [0000-0001-8789-8869], van der Schouw, Yvonne T. [0000-0002-4605-435X], Dahm, Christina C. [0000-0003-0481-2893], Franks, Paul W. [0000-0002-0520-7604], Heath, Alicia K. [0000-0001-6517-1300], Tong, Tammy Y. N. [0000-0002-0284-8959], Tsilidis, Konstantinos K. [0000-0002-8452-8472], Forouhi, Nita G. [0000-0002-5041-248X], Wareham, Nicholas J. [0000-0003-1422-2993]
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Single Nucleotide Polymorphisms
Organic chemistry
Genome-wide association study
Type 2 diabetes
VARIANTS
030204 cardiovascular system & hematology
Biochemistry
Endocrinology
Medical Conditions
Mathematical and Statistical Techniques
0302 clinical medicine
DESIGN
Risk Factors
Medicine and Health Sciences
Metabolites
VITAMIN-D SUPPLEMENTATION
030212 general & internal medicine
Prospective Studies
Vitamin D
11 Medical and Health Sciences
RISK
Diabetis
Statistics
Diabetes
Genomics
Vitamins
General Medicine
Metaanalysis
Middle Aged
Type 2 Diabetes
3. Good health
European Prospective Investigation into Cancer and Nutrition
Physical sciences
Chemistry
OBESITY
Endokrinologi och diabetes
Medicine
LIFE-STYLE
Female
Life Sciences & Biomedicine
Research Article
Adult
medicine.medical_specialty
Endocrine Disorders
DATABASE
Vitamina D
European Continental Ancestry Group
Single-nucleotide polymorphism
Endocrinology and Diabetes
Research and Analysis Methods
Lower risk
White People
Chemical compounds
03 medical and health sciences
Medicine
General & Internal
General & Internal Medicine
Internal medicine
Organic compounds
Diabetes Mellitus
Genome-Wide Association Studies
medicine
Vitamin D and neurology
Genetics
Humans
Statistical Methods
Science & Technology
business.industry
Biology and Life Sciences
Computational Biology
Human Genetics
Odds ratio
Mendelian Randomization Analysis
Genome Analysis
medicine.disease
Metabolism
Diabetes Mellitus
Type 2
Genetic Loci
Metabolic Disorders
Relative risk
Dietary Supplements
GENETIC-DETERMINANTS
business
Mathematics
Genètica
Genome-Wide Association Study
Zdroj: Zheng, J S, Luan, J, Sofianopoulou, E, Sharp, S J, Day, F R, Imamura, F, Gundersen, T E, Lotta, L A, Sluijs, I, Stewart, I D, Shah, R L, Van Der Schouw, Y T, Wheeler, E, Ardanaz, E, Boeing, H, Dorronsoro, M, Dahm, C C, Dimou, N, El-Fatouhi, D, Franks, P W, Fagherazzi, G, Grioni, S, Huerta, J M, Heath, A K, Hansen, L, Jenab, M, Jakszyn, P, Kaaks, R, Kühn, T, Khaw, K T, Laouali, N, Masala, G, Nilsson, P M, Overvad, K, Olsen, A, Panico, S, Ramón Quirós, J, Rolandsson, O, Rodríguez-Barranco, M, Sacerdote, C, Spijkerman, A M W, Tong, T Y N, Tumino, R, Tsilidis, K K, Danesh, J, Riboli, E, Butterworth, A S, Langenberg, C, Forouhi, N G & Wareham, N J 2020, ' The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations : A meta-analysis and Mendelian randomisation analysis ', PLOS Medicine, vol. 17, no. 10, e1003394 . https://doi.org/10.1371/journal.pmed.1003394
Dipòsit Digital de la UB
Universidad de Barcelona
Zheng, J-S, Luan, J, Sofianopoulou, E, Sharp, S J, Day, F R, Imamura, F, Gundersen, T E, Lotta, L A, Sluijs, I, Stewart, I D, Shah, R L, van der Schouw, Y T, Wheeler, E, Ardanaz, E, Boeing, H, Dorronsoro, M, Dahm, C C, Dimou, N, El-Fatouhi, D, Franks, P W, Fagherazzi, G, Grioni, S, Huerta, J M, Heath, A K, Hansen, L, Jenab, M, Jakszyn, P, Kaaks, R, Kühn, T, Khaw, K-T, Laouali, N, Masala, G, Nilsson, P M, Overvad, K, Olsen, A, Panico, S, Quirós, J R, Rolandsson, O, Rodríguez-Barranco, M, Sacerdote, C, Spijkerman, A M W, Tong, T Y N, Tumino, R, Tsilidis, K K, Danesh, J, Riboli, E, Butterworth, A S, Langenberg, C, Forouhi, N G & Wareham, N J 2020, ' The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations : A meta-analysis and Mendelian randomisation analysis ', PLOS Medicine, vol. 17, no. 10, e1003394 . https://doi.org/10.1371/journal.pmed.1003394
PLoS Medicine, Vol 17, Iss 10, p e1003394 (2020)
PLoS Medicine
Popis: Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals.
Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.
Databáze: OpenAIRE
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