Sabine R Zwakenberg1, Stephen Burgess2, Ivonne Sluijs1, Elisabete Weiderpass3, Joline W J Beulens4, Yvonne T van der Schouw5. 1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands. 2. Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. 3. International Agency for Research on Cancer, World Health Organization, Lyon, France. 4. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Department of Epidemiology & Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands. 5. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands. Electronic address: y.t.vanderschouw@umcutrecht.nl.
Abstract
BACKGROUND AND AIMS: Multiple observational studies and small-scale intervention studies suggest that high vitamin K intake is associated with improved markers for cardiovascular health. Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake. This study aims to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of CHD via a two-sample Mendelian Randomization approach. DESIGN: We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study, CARDIOGRAMplusC4D and the UK Biobank, resulting in 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using SNPs related to circulating phylloquinone and dp-ucMGP. We calculated a genetic risk score (GRS) including four SNPs (rs2108622, rs2192574, rs4645543 and rs6862071) related to circulating phylloquinone levels from a genome wide association study. Rs4236 was used as an instrumental variable for dp-ucMGP. Inverse-variance weighted (IVW) analysis was used to obtain Risk Ratios (RRs) for the causal relationship between phylloquinone and dp-ucMGP concentrations and CHD risk. RESULTS: Using the genetic score for circulating phylloquinone, we found that circulating phylloquinone was not causally related to CHD risk (RR 1.00 (95%-CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 (95%-CI: 0.93; 0.99) for every 10 μg/L decrease in dp-ucMGP. CONCLUSIONS: This study did not confirm a causal relationship between circulating phylloquinone and lower CHD risk. However, lower dp-ucMGP levels may be causally related with a decreased CHD risk. This inconsistent result may reflect the influence of menaquinones in the association with CHD.
BACKGROUND AND AIMS: Multiple observational studies and small-scale intervention studies suggest that high vitamin K intake is associated with improved markers for cardiovascular health. Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake. This study aims to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of CHD via a two-sample Mendelian Randomization approach. DESIGN: We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study, CARDIOGRAMplusC4D and the UK Biobank, resulting in 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using SNPs related to circulating phylloquinone and dp-ucMGP. We calculated a genetic risk score (GRS) including four SNPs (rs2108622, rs2192574, rs4645543 and rs6862071) related to circulating phylloquinone levels from a genome wide association study. Rs4236 was used as an instrumental variable for dp-ucMGP. Inverse-variance weighted (IVW) analysis was used to obtain Risk Ratios (RRs) for the causal relationship between phylloquinone and dp-ucMGP concentrations and CHD risk. RESULTS: Using the genetic score for circulating phylloquinone, we found that circulating phylloquinone was not causally related to CHD risk (RR 1.00 (95%-CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 (95%-CI: 0.93; 0.99) for every 10 μg/L decrease in dp-ucMGP. CONCLUSIONS: This study did not confirm a causal relationship between circulating phylloquinone and lower CHD risk. However, lower dp-ucMGP levels may be causally related with a decreased CHD risk. This inconsistent result may reflect the influence of menaquinones in the association with CHD.
Authors: Geertje W Dalmeijer; Yvonne T van der Schouw; Sarah L Booth; Pim A de Jong; Joline W J Beulens Journal: Arterioscler Thromb Vasc Biol Date: 2014-05-22 Impact factor: 8.311
Authors: Hassan S Dashti; M Kyla Shea; Caren E Smith; Toshiko Tanaka; Adela Hruby; Kris Richardson; Thomas J Wang; Mike A Nalls; Xiuqing Guo; Yongmei Liu; Jie Yao; Dalin Li; W Craig Johnson; Emelia J Benjamin; Stephen B Kritchevsky; David S Siscovick; José M Ordovás; Sarah L Booth Journal: Am J Clin Nutr Date: 2014-10-08 Impact factor: 7.045
Authors: Benjamin B Sun; Joseph C Maranville; James E Peters; David Stacey; James R Staley; James Blackshaw; Stephen Burgess; Tao Jiang; Ellie Paige; Praveen Surendran; Clare Oliver-Williams; Mihir A Kamat; Bram P Prins; Sheri K Wilcox; Erik S Zimmerman; An Chi; Narinder Bansal; Sarah L Spain; Angela M Wood; Nicholas W Morrell; John R Bradley; Nebojsa Janjic; David J Roberts; Willem H Ouwehand; John A Todd; Nicole Soranzo; Karsten Suhre; Dirk S Paul; Caroline S Fox; Robert M Plenge; John Danesh; Heiko Runz; Adam S Butterworth Journal: Nature Date: 2018-06-06 Impact factor: 49.962
Authors: Cornelia Weikert; Iris Trefflich; Juliane Menzel; Rima Obeid; Alessa Longree; Jutta Dierkes; Klaus Meyer; Isabelle Herter-Aeberli; Knut Mai; Gabriele I Stangl; Sandra M Müller; Tanja Schwerdtle; Alfonso Lampen; Klaus Abraham Journal: Dtsch Arztebl Int Date: 2020-08-31 Impact factor: 5.594
Authors: Ankita P Desai; Sahera Dirajlal-Fargo; Jared C Durieux; Heather Tribout; Danielle Labbato; Grace A McComsey Journal: Open Forum Infect Dis Date: 2021-07-29 Impact factor: 3.835
Authors: Essa Hariri; Nicholas Kassis; Jean-Pierre Iskandar; Leon J Schurgers; Anas Saad; Omar Abdelfattah; Agam Bansal; Toshiaki Isogai; Serge C Harb; Samir Kapadia Journal: Open Heart Date: 2021-11