Causal relationship between apolipoprotein B and risk of atherosclerotic cardiovascular disease: a mendelian randomization analysis

Health Inf Sci Syst. 2025 Jan 3;13(1):13. doi: 10.1007/s13755-024-00323-5. eCollection 2025 Dec.

Authors

Xiangyong Kong¹, Yanchen Cai¹, Yuwei Li¹, Ping Wang²

Affiliations

¹ School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093 China.
² Department of Nephrology and Rheumatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000 China.

PMID: 39758974
PMCID: PMC11698695 (available on 2026-12-01)
DOI: 10.1007/s13755-024-00323-5

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major threat to human life and health, and dyslipidemia with elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor, and in the optimal LDL-C scenario, apolipoprotein B (ApoB) has a more predictive value of ASCVD risk.

Methods: The study is a genome-wide association study (GWAS) based on a European population. A large GWAS dataset for atherosclerotic cardiovascular diseases was targeted, including coronary heart disease (CHD), ischemic stroke (IS), large-artery atherosclerotic stroke (ISL), small-vessel stroke (ISS), and myocardial infarction (MI). Univariate two-sample mendelian randomization (MR) analyses of ApoB and the above cardiovascular diseases were performed separately, and the association was assessed mainly using the inverse variance weighted (IVW) method, with confidence intervals for the superiority ratios set at 95%. In addition, the experiment was supplemented using MR-Egger, weighted model and weighted median (WM).

Results: Based on the results of univariate two-sample mendelian randomisation analysis, it was shown that there was a causal relationship between ApoB and CHD (OR = 1.710, 95% CI 1.529-1.912, P = 0.010), ISL (OR = 1.430, 95% CI 1.231-1.661, P = 2.714E-06), ISS (OR = 1.221, 95% CI 1.062-1.405, P = 0.005) were causally related to each other and the disease prevalence ratio was positively correlated with ApoB concentration.

Conclusion: This MR analysis demonstrated a causal relationship between ApoB and CHD, ISL, ISS, but not with the risk of developing IS and MI, which further validated the relationship between ApoB and the risk of ASCVD, and contributed to a better understanding of the genetic impact of ApoB on ASCVD, and to a certain extent, could improve the management of ApoB and reduce the prevalence of ASCVD.

Keywords: Apolipoprotein B; Atherosclerotic cardiovascular disease; Mendelian randomization; Risk factors.

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