Dataset Information

Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

ABSTRACT: Background: Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS using bidirectional and multivariable Mendelian randomization (MR) studies. Methods: Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were performed to evaluate the effect of HF on IS or the effect of IS on HF. Results: Two-sample MR analysis showed causal effects of HF on IS of all causes [odds ratio (OR) = 1.555, 95% confidence interval (CI): 1.343-1.799, p = 3.35 × 10-9] and large artery atherosclerosis stroke (LAS) (OR = 1.678, 95% CI: 1.044-2.696, p = 3.03 × 10-5), while there was a suggestive effect of HF on cardioembolic stroke (CES) (OR = 3.355, 95% CI: 1.031-10.919, p = 0.044). Genetically predicted HF was not associated with small artery occlusion stroke. Bidirectional MR analysis showed causal effects of IS of all causes (OR = 1.211, 95% CI: 1.040-1.410, p = 0.014) and CES (OR = 1.277, 95% CI: 1.213-1.344, p = 6.73 × 10-21) on HF, while there were no causal effects of LAS on HF. Conclusion: This MR analysis provided evidence of the causal links between genetically predicted HF and IS. Subgroup analysis highlighted the causal or suggestive relationship between genetically predicted HF and LAS or CES. The potential causal links need further investigation with genetic information about other ancestries or etiologies of HF.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8666512 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

Zhang Luyang L Liu Weishi W Sun Wenxian W Wang Xin X Tian Mengke M Pei Lu-Lu LL Liu Kai K Liang Jing J Zhou Lue L Lu Jie J Ning Mingming M Buonanno Ferdinando S FS Xu Yuming Y Song Bo B

Frontiers in genetics 20211129

<b>Background:</b> Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS using bidirectional and multivariable Mendelian randomization (MR) studies. <b>Methods:</b> Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were perfor ...[more]

PMID: 34912375

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Project description:BackgroundIschemic Heart Disease (IHD) is a leading cause of morbidity and mortality worldwide. Hypercholesterolaemia, a metabolic syndrome distinguished by elevated cholesterol levels, is positively correlated with IHD, yet the precise causal relationship between these two health conditions remains to be clearly defined.MethodsWe conducted a two-sample MR analysis using genetic variants associated with hypercholesterolemia and IHD. Various statistical techniques including MR-Egger, Weighted Median, Inverse Variance Weighted (IVW), Simple Mode, and Weighted Mode were employed. We also performed sensitivity analyses to assess pleiotropy, heterogeneity, and influence of individual SNPs. Furthermore, genetic co-localization analysis was performed to identify shared genes between hypercholesterolemia and IHD.ResultsOur MR study illuminated a bidirectional causal relationship between hypercholesterolaemia and ischaemic heart disease. Utilising the IVW with multiplicative random effects, upon considering IHD as the outcome, we identified an OR of 2.27 (95% CI: 1.91-2.70, p = 1.68 × 10-20). Conversely, when hypercholesterolaemia was viewed as the outcome, the OR detected was 1.80 (95% CI: 1.58-2.05, p = 2.79 × 10-19). These findings remained consistent across various MR methods and sensitivity analyses. Additionally, our research pinpointed four co-localised genes CELSR2, PCSK9, LPA, and APOE as integral candidates implicated in the pathogenesis of both conditions, thereby suggesting shared common genetic causal variants and offering potential targets for innovative therapeutic strategies.Conclusionbidirectional MR studies reveal genetic evidence of a potential causal link between hypercholesterolaemia and IHD. Notably, these findings also lend credence to the less traditional hypothesis that IHD may instigate hypercholesterolaemia episodes. Moreover, co-localisation analyses intimate the presence of shared genetic causal variants, paving the way for the development of new therapeutic strategies.

Dataset Information

Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

Publications

Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

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