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The Causal Role of Apolipoprotein B/A1 Ratio in Coronary Heart Disease and Ischemic Stroke: A Mendelian Randomization Study

Li, H.; Wang, J. B.; Chen, W. H.; Chen, J. Y.; Li, Y.; Li, B. X.; Wang, N.; Liu, L.; Song, H. Z.

2025-06-12 cardiovascular medicine
10.1101/2025.06.11.25328879 medRxiv
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Background/AimsAlthough epidemiological analyses have suggested a link between a heightened ratio of apolipoprotein (Apo) B/A1 and atherosclerosis (ATS), the exact causative connection between ApoB/A1 and coronary heart disease (CHD) and ischemic stroke (IS) onset is ambiguous. Accordingly, our objective was to investigate the causal interaction between ApoB/A1 and both CHD and IS. MethodsA Mendelian randomization (MR) approach was applied, utilizing data from two samples to infer causality. Extensive genetic information concerning ApoB/A1 was retrieved from a recent genome-wide association study (GWAS) encompassing 115,082 participants of European ancestry. The SNP datasets associated with CHD and IS were downloaded by accessing the IEU GWAS database. The MR approach was deployed to determine causal impacts and identify pleiotropy. ResultsOur results reveal that elevated ApoB/A1 was linked with heightened risks of CHD (OR: 1.008; 95% CI: 1.005-1.010; P < 0.001) and IS (OR: 1.332; 95% CI: 1.112-1.595; P = 0.002). ConclusionsOur findings confirm the causal relationship between a genetic predisposition for an elevated ApoB/A1 and heightened CHD and IS risks. To conclude, ApoB/A1 could be a potential therapeutic target for these two diseases.

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