|ZWAKENBERG, SABINE - University Medical Center Utrecht|
|REMMELZWAAL, SHARON - Vu University Medical Center|
|BEULENS, JOLINE - Vu University Medical Center|
|BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|BURGESS, STEPHEN - University Of Cambridge|
|DASHTI, HASSAN - Massachusetts General Hospital|
|IMAMURA, FUMIAKI - University Of Cambridge|
|FESKENS, EDITH - Wageningen University|
|VAN DER SCHOUW, YVONNE - University Medical Center Utrecht|
|SLUIJS, IVONNE - University Medical Center Utrecht|
Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2018
Publication Date: 1/2/2019
Citation: Zwakenberg, S.R., Remmelzwaal, S., Beulens, J.W., Booth, S.L., Burgess, S., Dashti, H.S., Imamura, F., Feskens, E.J., Van Der Schouw, Y.T., Sluijs, I. 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.
Interpretive Summary: This study aims to investigate the relationship among circulating phylloquinone (vitamin K) concentrations and type 2 diabetes using a validated data analysis approach that can infer causality. We used data from about 70,000 participants with type 2 diabetes from three European cohorts to calculate a genetic risk score that used the four genetic variants that are associated with circulating phylloquinone concentrations. This genetic risk score was then used to estimate the risk between low circulating phylloquinone concentrations and higher risk of type 2 diabetes. We found that the concentration of circulating phylloquinone that was predicted by the genetic variants of the participants was associated with lower risk of type 2 diabetes. 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.
Technical Abstract: This study aims to investigate the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes using a Mendelian Randomization (MR) approach. We used data from thee cohorts: 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 type 2 diabetes cases. We calculated a weighted genetic risk score including four genetic variants previously found to associate 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 concentration of circulating phylloquinone was associated with lower risk of type 2 diabetes with a RR of 0.93 (95% confidence interval: 0.89;0.97) per every 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.