Genetically predicted osteoprotegerin levels and the risk of cardiovascular diseases: A Mendelian randomization study

Yanchen Zhu; Yichao Wang; Xiaoyuan Liu; Yahui Wang; Zhaorui Cui; Fani Liu; Jiqiang Hu

doi:10.1016/j.ijcard.2023.131233

Genetically predicted osteoprotegerin levels and the risk of cardiovascular diseases: A Mendelian randomization study

Int J Cardiol. 2023 Nov 1:390:131233. doi: 10.1016/j.ijcard.2023.131233. Epub 2023 Jul 31.

Authors

Yanchen Zhu¹, Yichao Wang², Xiaoyuan Liu³, Yahui Wang¹, Zhaorui Cui¹, Fani Liu¹, Jiqiang Hu⁴

Affiliations

¹ Cardiology Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China.
² Laboratory Department, Jilin Provincial Hospital of Integrated TCM and Western Medicine, Jilin, China.
³ Laboratory Department, Jilin Provincial Hospital of Integrated TCM and Western Medicine, Jilin, China. Electronic address: 498406452@qq.com.
⁴ Cardiology Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China. Electronic address: hujiqiang0923@163.com.

PMID: 37532154
DOI: 10.1016/j.ijcard.2023.131233

Abstract

Purpose: The relationship between circulating osteoprotegerin (OPG) levels and the risk of cardiovascular diseases (CVDs) has been the subject of conflicting results in previous observational and experimental studies. To assess the causal effect of genetically predicted OPG levels on the risk of a wide range of CVDs, we used the Mendelian randomization design.

Design: We initially extracted information of genetic variants on OPG levels and their corresponding effect values from the summary data based on the European ancestry genome-wide association study. Subsequently, we performed two-sample Mendelian randomization analyses to assess the causal effect of genetically predicted OPG levels on CVDs by using inverse variance weighting (IVW), MR-Egger, weighted median, and MR-PRESSO methods. We also conducted sensitivity analyzes as well as complementary analyses with a more relaxed threshold for the exposure genetic instrumental variable (P < 5 × 10^-6) to test the robustness of our results.

Results: Our results indicated that genetically predicted OPG levels causally reduce the risk of atrial fibrillation (IVW OR = 0.84; 95% CI = 0.72-0.98; P = 0.0241), myocardial infarction(IVW OR = 0.89; 95% CI = 0.80-0.98; P = 0.0173) and coronary heart disease (IVW: OR = 0.90; 95% CI = 0.82-0.99; P = 0.0286). Further complementary analyses also confirmed the above results remain robust and we also identified a potential causal association of OPG levels with a reduced risk of hypertensive diseases(IVW OR = 0.94;95% CI = 0.88-1.00; P = 0.0394).

Conclusion: This study provides compelling evidence for a causal relationship between genetically predicted OPG levels and risk reduction of coronary heart disease, myocardial infarction, and atrial fibrillation, indicating that OPG could potentially serve as a cardiovascular risk marker in clinical practice.

Keywords: Cardiovascular diseases; Causality; Genetic variants; Mendelian randomization; Osteoprotegerin.

Publication types

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MeSH terms

Atrial Fibrillation*
Cardiovascular Diseases* / diagnosis
Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Myocardial Infarction*
Osteoprotegerin / genetics

Substances

Osteoprotegerin
TNFRSF11B protein, human