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27-03-2024 | Coronary Heart Disease | Research

Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study

Authors: Yi-Ming Shi, Dian Ou, Jia-Ting Li, Le Bao, Xiao-Dan Liu, Wei Zhang, Huang Ding

Published in: Cardiovascular Toxicology | Issue 4/2024

Abstract

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823–0.958, p = 2.3 × 10^–3], Coronary heart disease [IVW OR 0.950,95% CI: 0.924–0.976, p = 2.0 × 10^–4] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931–0.991, p = 1.1 × 10^–2]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006–1.060, p = 1.8 × 10^–2]. (Bonferroni threshold p < 0.0026, P_FDR < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized.

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Title: Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study
Authors: Yi-Ming Shi
Dian Ou
Jia-Ting Li
Le Bao
Xiao-Dan Liu
Wei Zhang
Huang Ding
Publication date: 27-03-2024
Publisher: Springer US
Keywords: Coronary Heart Disease
Heart Failure
Published in: Cardiovascular Toxicology / Issue 4/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-024-09846-5

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