TY - JOUR AU - Zheng, Ju-Sheng AU - Luan, Jian'an AU - Sofianopoulou, Eleni AU - Sharp, Stephen J AU - Day, Felix R AU - Imamura, Fumiaki AU - Gundersen, Thomas E AU - Lotta, Luca A AU - Sluijs, Ivonne AU - Stewart, Isobel D AU - Shah, Rupal L AU - van der Schouw, Yvonne T AU - Wheeler, Eleanor AU - Ardanaz, Eva AU - Boeing, Heiner AU - Dorronsoro, Miren AU - Dahm, Christina C AU - Dimou, Niki AU - El-Fatouhi, Douae AU - Franks, Paul W AU - Fagherazzi, Guy AU - Grioni, Sara AU - Huerta, José María AU - Heath, Alicia K AU - Hansen, Louise AU - Jenab, Mazda AU - Jakszyn, Paula AU - Kaaks, Rudolf AU - Kühn, Tilman AU - Khaw, Kay-Tee AU - Laouali, Nasser AU - Masala, Giovanna AU - Nilsson, Peter M AU - Overvad, Kim AU - Olsen, Anja AU - Panico, Salvatore AU - Quirós, J Ramón AU - Rolandsson, Olov AU - Rodríguez-Barranco, Miguel AU - Sacerdote, Carlotta AU - Spijkerman, Annemieke M W AU - Tong, Tammy Y N AU - Tumino, Rosario AU - Tsilidis, Konstantinos K AU - Danesh, John AU - Riboli, Elio AU - Butterworth, Adam S AU - Langenberg, Claudia AU - Forouhi, Nita G AU - Wareham, Nicholas J TI - The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis. JO - PLoS medicine VL - 17 IS - 10 SN - 1549-1676 CY - Lawrence, Kan. PB - PLoS M1 - DKFZ-2020-02218 SP - e1003394 - PY - 2020 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 LB - PUB:(DE-HGF)16 C6 - pmid:33064751 DO - DOI:10.1371/journal.pmed.1003394 UR - https://inrepo02.dkfz.de/record/164050 ER -