Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: A Mendelian Randomization Study.
Beulens, Joline WJ
Booth, Sarah L
Feskens, Edith JM
van der Schouw, Yvonne T
American Diabetes Association
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Zwakenberg, S. R., Remmelzwaal, S., Beulens, J. W., Booth, S. L., Burgess, S., Dashti, H. S., Imamura, F., et al. (2019). Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: A Mendelian Randomization Study.. Diabetes, 68 (1), 220-225. https://doi.org/10.2337/db18-0543
This study investigated the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes by using a Mendelian randomization (MR) approach. We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM), and the UK Biobank, resulting in 69,647 subjects with type 2 diabetes. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations. Inverse-variance weighted analysis was used to obtain a risk ratio (RR) for the causal relation between circulating phylloquinone concentrations and risk of type 2 diabetes. Presence of pleiotropy and the robustness of the results were assessed using MR-Egger and weighted-median analyses. Genetically predicted concentrations of circulating phylloquinone were associated with lower risk of type 2 diabetes with an RR of 0.93 (95% CI 0.89; 0.97) per every natural logarithm (Ln)-nmol/L-unit increase in circulating phylloquinone. The MR-Egger and weighted median analyses showed RRs of 0.94 (0.86; 1.02) and 0.93 (0.88; 0.98), respectively, indicating no pleiotropy. In conclusion, our study supports that higher circulating phylloquinone may be causally related with lower risk of type 2 diabetes, highlighting the importance of sufficient phylloquinone in the human diet.
Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Vitamin K 1, Risk Factors, Cohort Studies, Prospective Studies, Genotype, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis
Funding for the EPIC-InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). This research has been conducted using the UK Biobank Resource (application number 9161, 9905, 12885 and 20684). SRZ and JWJB are supported by the Senior Dr. Dekker grant (2013T120) from The Dutch Heart Foundation. IS is supported by a personal Dr. Dekker Junior Postdoctoral grant (2015T19) from The Dutch Heart Foundation. FI is supported by MRC Epidemiology Unit Core Grant (MC_UU_12015/5). SLB is partially supported by the USDA Agricultural Research Service cooperative agreement 58-1950-7-707.
Medical Research Council (MC_UU_12015/5)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
Medical Research Council (MC_UU_00002/7)
External DOI: https://doi.org/10.2337/db18-0543
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286386