Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study

Sabine R. Zwakenberg, Sharon Remmelzwaal, Joline W. J. Beulens, Sarah L. Booth, Stephen Burgess, Hassan S. Dashti, Fumiaki Imamura, Edith J. M. Feskens, Yvonne T. van der Schouw, Ivonne Sluijs

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
LanguageEnglish
Pages220-225
JournalDiabetes
Volume68
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Zwakenberg, Sabine R. ; Remmelzwaal, Sharon ; Beulens, Joline W. J. ; Booth, Sarah L. ; Burgess, Stephen ; Dashti, Hassan S. ; Imamura, Fumiaki ; Feskens, Edith J. M. ; van der Schouw, Yvonne T. ; Sluijs, Ivonne. / Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study. In: Diabetes. 2019 ; Vol. 68, No. 1. pp. 220-225.
@article{947e596f417648f88de60b567baef5ea,
title = "Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study",
abstract = "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.",
author = "Zwakenberg, {Sabine R.} and Sharon Remmelzwaal and Beulens, {Joline W. J.} and Booth, {Sarah L.} and Stephen Burgess and Dashti, {Hassan S.} and Fumiaki Imamura and Feskens, {Edith J. M.} and {van der Schouw}, {Yvonne T.} and Ivonne Sluijs",
year = "2019",
doi = "10.2337/db18-0543",
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pages = "220--225",
journal = "Diabetes",
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Zwakenberg, SR, Remmelzwaal, S, Beulens, JWJ, Booth, SL, Burgess, S, Dashti, HS, Imamura, F, Feskens, EJM, van der Schouw, YT & Sluijs, I 2019, 'Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study', Diabetes, vol. 68, no. 1, pp. 220-225. https://doi.org/10.2337/db18-0543

Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study. / Zwakenberg, Sabine R.; Remmelzwaal, Sharon; Beulens, Joline W. J.; Booth, Sarah L.; Burgess, Stephen; Dashti, Hassan S.; Imamura, Fumiaki; Feskens, Edith J. M.; van der Schouw, Yvonne T.; Sluijs, Ivonne.

In: Diabetes, Vol. 68, No. 1, 2019, p. 220-225.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Circulating phylloquinone concentrations and risk of type 2 diabetes: A mendelian randomization study

AU - Zwakenberg, Sabine R.

AU - Remmelzwaal, Sharon

AU - Beulens, Joline W. J.

AU - Booth, Sarah L.

AU - Burgess, Stephen

AU - Dashti, Hassan S.

AU - Imamura, Fumiaki

AU - Feskens, Edith J. M.

AU - van der Schouw, Yvonne T.

AU - Sluijs, Ivonne

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N2 - 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.

AB - 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.

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