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@article{Zheng:2020:10.1371/journal.pmed.1003394,
author = {Zheng, J-S and Luan, J and Sofianopoulou, E and Sharp, SJ and Day, FR and Imamura, F and Gundersen, TE and Lotta, LA and Sluijs, I and Stewart, ID and Shah, RL and van, der Schouw YT and Wheeler, E and Ardanaz, E and Boeing, H and Dorronsoro, M and Dahm, CC and Dimou, N and El-Fatouhi, D and Franks, PW and Fagherazzi, G and Grioni, S and Huerta, JM and Heath, AK and Hansen, L and Jenab, M and Jakszyn, P and Kaaks, R and Kuehn, T and Khaw, K-T and Laouali, N and Masala, G and Nilsson, PM and Overvad, K and Olsen, A and Panico, S and Quiros, JR and Rolandsson, O and Rodriguez-Barranco, M and Sacerdote, C and Spijkerman, AMW and Tong, TYN and Tumino, R and Tsilidis, KK and Danesh, J and Riboli, E and Butterworth, AS and Langenberg, C and Forouhi, NG and Wareham, NJ},
doi = {10.1371/journal.pmed.1003394},
journal = {PLoS Medicine},
pages = {1--21},
title = {The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis},
url = {http://dx.doi.org/10.1371/journal.pmed.1003394},
volume = {17},
year = {2020}
}

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TY  - JOUR
AB  - BackgroundPrior 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 findingsWe 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 (R
AU  - Zheng,J-S
AU  - Luan,J
AU  - Sofianopoulou,E
AU  - Sharp,SJ
AU  - Day,FR
AU  - Imamura,F
AU  - Gundersen,TE
AU  - Lotta,LA
AU  - Sluijs,I
AU  - Stewart,ID
AU  - Shah,RL
AU  - van,der Schouw YT
AU  - Wheeler,E
AU  - Ardanaz,E
AU  - Boeing,H
AU  - Dorronsoro,M
AU  - Dahm,CC
AU  - Dimou,N
AU  - El-Fatouhi,D
AU  - Franks,PW
AU  - Fagherazzi,G
AU  - Grioni,S
AU  - Huerta,JM
AU  - Heath,AK
AU  - Hansen,L
AU  - Jenab,M
AU  - Jakszyn,P
AU  - Kaaks,R
AU  - Kuehn,T
AU  - Khaw,K-T
AU  - Laouali,N
AU  - Masala,G
AU  - Nilsson,PM
AU  - Overvad,K
AU  - Olsen,A
AU  - Panico,S
AU  - Quiros,JR
AU  - Rolandsson,O
AU  - Rodriguez-Barranco,M
AU  - Sacerdote,C
AU  - Spijkerman,AMW
AU  - Tong,TYN
AU  - Tumino,R
AU  - Tsilidis,KK
AU  - Danesh,J
AU  - Riboli,E
AU  - Butterworth,AS
AU  - Langenberg,C
AU  - Forouhi,NG
AU  - Wareham,NJ
DO  - 10.1371/journal.pmed.1003394
EP  - 21
PY  - 2020///
SN  - 1549-1277
SP  - 1
TI  - The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis
T2  - PLoS Medicine
UR  - http://dx.doi.org/10.1371/journal.pmed.1003394
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000582196300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003394
UR  - http://hdl.handle.net/10044/1/87781
VL  - 17
ER  -

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