Dataset Information

Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study.

ABSTRACT: Background: The causal evidence of the triglyceride-glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking. Methods: A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive control, and external verification were utilized. Outcomes include major outcomes [overall CVD, ischemic heart diseases (IHD), and cerebrovascular diseases (CED)] and minor outcomes [angina pectoris (AP), acute myocardial infarction (AMI), chronic IHD (CIHD), heart failure (HF), hemorrhagic stroke (HS), and ischemic stroke (IS)]. Results: The TyG index significantly increased the risk of overall CVD [OR (95% CI): 1.20 (1.14-1.25)], IHD [OR (95% CI): 1.22 (1.15-1.29)], CED [OR (95% CI): 1.14 (1.05-1.23)], AP [OR (95% CI): 1.29 (1.20-1.39)], AMI [OR (95% CI): 1.27 (1.16-1.39)], CIHD [OR (95% CI): 1.21 (1.13-1.29)], and IS [OR (95% CI): 1.22 (1.06-1.40)]. Joint exposure to genetically higher GLU and TG was significantly associated with a higher risk of overall CVD [OR (95% CI): 1.17 (1.12-1.23)] and IHD [OR (95% CI): 1.22 (1.16-1.29)], but not with CED. The effect of GLU and TG was independent of each other genetically and presented dose-response effects in bivariate meta-regression analysis. Conclusions: Lifelong genetic exposure to higher GLU and TG was jointly associated with higher cardiac metabolic risk while the TyG index additionally associated with several cerebrovascular diseases. The TyG index could serve as a more sensitive pre-diagnostic indicator for CVD while the joint GLU and TG could offer a quantitative risk for cardiac metabolic outcomes.

SUBMITTER: Si S

PROVIDER: S-EPMC7863795 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study.

Si Shucheng S Li Jiqing J Li Yunxia Y Li Wenchao W Chen Xiaolu X Yuan Tonghui T Liu Congcong C Li Hongkai H Hou Lei L Wang Bojie B Xue Fuzhong F

Frontiers in cardiovascular medicine 20210122

<b>Background:</b> The causal evidence of the triglyceride-glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking. <b>Methods:</b> A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive ...[more]

PMID: 33553250

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Project description:BackgroundCausal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD.MethodsTwo-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed.ResultsApolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well.ConclusionThe remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Project description:Background Increasing incidences of both atrial fibrillation (AF) and cancer have been observed in recent years. However, the casual association of both serious conditions has been scarcely evaluated and is considered to be a blank slate in cardio-oncology. Thus, we introduced Mendelian randomization (MR) methods to estimate the effects of AF on cancer risks. Methods We performed univariable and multivariable two-sample MR analyses to evaluate the effects of AF on the risk of 19 site-specific types of cancer. This MR study was conducted based on 111 independent AF-associated genetic instruments from genome-wide association studies and summarized-level data from corresponding cancer consortia. Multiple sensitivity analyses, including the leave-one-out analysis, MR-Egger regression, and MR-PRESSO tests, were further performed to examine the potential directional pleiotropic effects. Functional annotation was performed for common differentially expressed genes of AF and prostate cancer (PCA). Results A total of 6,777,155 European-descent people, including 533,725 cases and 6,243,430 controls, were included in the present MR analysis. Univariable MR analyses demonstrated a causal effect of AF on the incidence of PCA [odds ratio (OR): 0.96; 95% confidence interval (CI) 0.92–0.99, p = 0.01], and the causal effect remained significant (OR: 0.65; 95% CI 0.47–0.90, p = 0.01) after adjusting for potential confounders through the multivariable MR approach. However, no casual associations between AF and the other 18 site-specific cancer risks were observed (all p-values were > 0.05). The consistency of outcomes across complementary sensitivity MR methods further supported the causality. The functional analysis emphasized the essential role of antioxidant and xenobiotic catabolic processes in AF and PCA. Conclusion Contrary to the findings of several previous observational studies, our comprehensive MR analyses did not corroborate a causal role for AF in increasing the risk of various types of cancer. They did, however, demonstrate that AF may decrease the risk of PCA. Studies from larger sample sizes and individuals with different ethnic backgrounds are required to further support our conclusions.

Dataset Information

Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study.

Publications

Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study.

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