RT Journal Article
T1 The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.
A1 Zheng, Ju-Sheng
A1 Luan, Jian'an
A1 Sofianopoulou, Eleni
A1 Sharp, Stephen J
A1 Day, Felix R
A1 Imamura, Fumiaki
A1 Gundersen, Thomas E
A1 Lotta, Luca A
A1 Sluijs, Ivonne
A1 Stewart, Isobel D
A1 Shah, Rupal L
A1 van der Schouw, Yvonne T
A1 Wheeler, Eleanor
A1 Ardanaz, Eva
A1 Boeing, Heiner
A1 Dorronsoro, Miren
A1 Dahm, Christina C
A1 Dimou, Niki
A1 El-Fatouhi, Douae
A1 Franks, Paul W
A1 Fagherazzi, Guy
A1 Grioni, Sara
A1 Huerta, José María
A1 Heath, Alicia K
A1 Hansen, Louise
A1 Jenab, Mazda
A1 Jakszyn, Paula
A1 Kaaks, Rudolf
A1 Kühn, Tilman
A1 Khaw, Kay-Tee
A1 Laouali, Nasser
A1 Masala, Giovanna
A1 Nilsson, Peter M
A1 Overvad, Kim
A1 Olsen, Anja
A1 Panico, Salvatore
A1 Quiros, J Ramon
A1 Rolandsson, Olov
A1 Rodriguez-Barranco, Miguel
A1 Sacerdote, Carlotta
A1 Spijkerman, Annemieke M W
A1 Tong, Tammy Y N
A1 Tumino, Rosario
A1 Tsilidis, Konstantinos K
A1 Danesh, John
A1 Riboli, Elio
A1 Butterworth, Adam S
A1 Langenberg, Claudia
A1 Forouhi, Nita G
A1 Wareham, Nicholas J
K1 Adult
K1 Diabetes Mellitus, Type 2
K1 Dietary Supplements
K1 Female
AB 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. 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  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.
PB Public Library of Science
YR 2020
FD 2020-09-11
LK http://hdl.handle.net/10668/16431
UL http://hdl.handle.net/10668/16431
LA en
NO Zheng JS, Luan J, Sofianopoulou E, Sharp SJ, Day FR, Imamura F, et al. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis. PLoS Med. 2020 Oct 16;17(10):e1003394.
DS RISalud
RD Mar 14, 2025