Dataset Information

Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study.

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.

SUBMITTER: Zwakenberg SR

PROVIDER: S-EPMC7612948 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundMajor depressive disorder (MDD) is a highly heterogeneous mental illness and a major public health problem worldwide. A large number of observational studies have demonstrated a clear association between MDD and coronary heart disease (CHD), and some studies have even suggested that the relationship is bidirectional. However, it was unknown whether any causal relationship existed between them and whether causality was bidirectional in such an instance. Thus, we aimed to determine whether there is a bidirectional causal relationship between major depressive disorders and coronary heart disease.MethodsOur two-sample Bidirectional Mendelian Randomization Study consisted of two parts: forward MR analysis regarded MDD as exposure and CHD as the outcome, and reverse MR analysis considered CHD as exposure and MDD as the outcome. Summary data on MDD and CHD were obtained from the IEU Open GWAS database. After screening criteria(P < [Formula: see text]), 47 MDD-associated SNPs and 39 CHD-associated SNPs were identified. The inverse-variance weighted (IVW) method, ME-Egger regression, and weighted median method were used to estimate causality. In addition, sensitivity methods, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out method, were applied to ensure the robustness of causal estimation.ResultsBased on the MR-Egger regression intercept test results, there did not appear to be any horizontal pleiotropy in this study (MDD: intercept = -0.0000376, P = 0.9996; CHD: intercept = -0.0002698, P = 0.920). Accordingly, IVW results suggested consistent estimates of causal effect values. The results showed that people with MDD increased the risk of CHD by 14.7% compared with those without MDD (OR = 1.147, 95%CI: 1.045-1.249, P = 0.009). But there was no direct evidence that CHD would increase the risk of MDD(OR = 1.008, 95%CI: 0.985-1.031, P = 0.490). The heterogeneity test and funnel plot showed no heterogeneity in 47 SNPs of MDD (Q = 42.28, [Formula: see text]=0, P = 0.629), but there was heterogeneity in 39 SNPs of CHD (Q = 62.48, [Formula: see text]=39.18%, P = 0.007). The leave-one-out method failed to identify instances where a single SNP was either biased toward or dependent on the causation.ConclusionOur study supports a one-way causal relationship between MDD and CHD, but there is no bidirectional causal relationship. MDD increases the risk of CHD, but there is no evidence that CHD increases the risk of MDD. Therefore, the influence of psychological factors should also be considered in the prevention and treatment of CHD. For MDD patients, it is necessary to prevent cardiovascular diseases.