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

Korean Circulation Journal 2020년 50권 10호 p.940 ~ 948
이수현, 이지영, 김건희, 정금지, 이선미, 김현창, 지선하,
소속 상세정보
이수현 ( Lee Su-Hyun ) - Yonsei University Graduate School of Public Health Department of Epidemiology and Health Promotion
이지영 ( Lee Ji-Young ) - Yonsei University Graduate School of Public Health Department of Epidemiology and Health Promotion
김건희 ( Kim Guen-Hui ) - Yonsei University Graduate School of Public Health Department of Epidemiology and Health Promotion
정금지 ( Jung Keum-Ji ) - Yonsei University Graduate School of Public Health Department of Epidemiology and Health Promotion
이선미 ( Lee Sun-Mi ) - National Health Insurance Service Health Insurance Policy Research Institute
김현창 ( Kim Hyeon-Chang ) - Yonsei University College of Medicine Department of Preventive Medicine
지선하 ( Jee Sun-Ha ) - Yonsei University Graduate School of Public Health Department of Epidemiology and Health Promotion

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.

키워드

Mendelian randomization analysis; Lipid; Ischemic heart disease

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