Dataset Information

Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease.

ABSTRACT: BACKGROUND AND OBJECTIVES:Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population. METHODS:A 2-sample Mendelian randomization (MR) study, using the genetic variants associated with lipid levels as the instrumental variables was performed. Genetic variants significantly associated with lipid concentrations were obtained from the Korean Genome and Epidemiology Study (n=35,000), and the same variants on IHD were obtained from the Korean Cancer Prevention Study-II (n=13,855). Inverse variance weighting (IVW), weighted median, and MR-Egger approaches were used to assess the causal association between lipid levels and IHD. Radial MR methods were applied to remove outliers subject to pleiotropic bias. RESULTS:Causal association between low-density lipoprotein-cholesterol (LDL-C) and IHD was observed in the IVW method (odds ratio, 1.013; 95% confidence interval, 1.007-1.109). However, high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) did not show causal association with IHD. In the Radial MR analysis of the relationship between HDL-C, TG and IHD, outliers were detected. Interestingly, after removing the outliers, a causal association between TG and IHD was found. CONCLUSIONS:High levels LDL-C and TG were causally associated with increased IHD risk in a Korean population, these results are potentially useful as evidence of a significant causal relationship.

SUBMITTER: Lee SH

PROVIDER: S-EPMC7515757 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease.

Lee Su Hyun SH Lee Ji Young JY Kim Guen Hui GH Jung Keum Ji KJ Lee Sunmi S Kim Hyeon Chang HC Jee Sun Ha SH

Korean circulation journal 20200713 10

<h4>Background and objectives</h4>Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population.<h4>Methods</h4>A 2-sample Mendelian randomization (MR) study, usin ...[more]

PMID: 32812402

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Project description:BackgroundThe cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs).MethodsGenetic variants strongly (p < 5 × 10-8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649).ResultsGenetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was - 1.173 (95% confidence interval - 2.214 to - 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs.ConclusionsOur study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

Project description:Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer's disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations. Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK's Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results. Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis. Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.

Dataset Information

Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease.

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Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease.

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