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Meta-Analysis
. 2022 Jun 27:12:884298.
doi: 10.3389/fcimb.2022.884298. eCollection 2022.

Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases

Jiang-Shan Tan  1 , Jia-Meng Ren  2 , Luyun Fan  3 , Yuhao Wei  4 , Song Hu  5 , Sheng-Song Zhu  5 , Yanmin Yang  1 , Jun Cai  3
Affiliations
Meta-Analysis

Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases

Jiang-Shan Tan et al. Front Cell Infect Microbiol. .

Abstract

Background: Accumulating evidence has indicated that persistent human cytomegalovirus (HCMV) infection is associated with several cardiovascular diseases including atherosclerosis and coronary artery disease. However, whether there is a causal association between the level of anti-HCMV immune response and the risk of cardiovascular diseases remains unknown.

Methods: Single-nucleotide polymorphisms associated with anti-cytomegalovirus immunoglobulin (Ig) G levels were used as instrumental variables to estimate the causal effect of anti-cytomegalovirus IgG levels on 9 cardiovascular diseases (including atrial fibrillation, coronary artery disease, hypertension, heart failure, peripheral artery disease, pulmonary embolism, deep vein thrombosis of the lower extremities, rheumatic valve diseases, and non-rheumatic valve diseases). For each cardiovascular disease, Mendelian randomization (MR) analyses were performed. Inverse variance-weighted meta-analysis (IVW) with a random-effects model was used as a principal analysis. In addition to this, the weighted median approach and MR-Egger method were used for further sensitivity analysis.

Results: In the IVW analysis, genetically predicted anti-cytomegalovirus IgG levels were suggestively associated with coronary artery disease with an odds ratio (OR) of 1.076 [95% CI, 1.009-1.147; p = 0.025], peripheral artery disease (OR 1.709; 95% CI, 1.039-2.812; p = 0.035), and deep vein thrombosis (OR 1.002; 95% CI, 1.000-1.004; p = 0.025). In the further analysis, similar causal associations were obtained from weighted median analysis and MR-Egger analysis with lower precision. No notable heterogeneities and horizontal pleiotropies were observed (p > 0.05).

Conclusions/interpretation: Our findings first provide direct evidence that genetic predisposition of anti-cytomegalovirus IgG levels increases the risk of coronary artery disease, peripheral artery disease, and deep vein thrombosis.

Keywords: Mendelian randomization; cardiovascular disease; cytomegalovirus; immunology; risk.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of an MR analysis. We selected SNPs associated with anti-cytomegalovirus IgG levels, and the corresponding effect for these SNPs was estimated based on the risk of 9 cardiovascular diseases. Because of the randomization and independence of alleles at meiosis, MR is a powerfully predictive tool to assess causal relationships with no bias inherent to observational study designs. CAD, coronary artery disease; PAD, Peripheral artery disease; DVT, deep vein thrombosis; MR, Mendelian randomization; SNPs, single-nucleotide polymorphisms.
Figure 2
Figure 2
Results of the Mendelian randomization analysis investigating the association of genetically proxied anti-cytomegalovirus IgG levels and risk of 9 cardiovascular diseases. Forest plot showing inverse variance-weighted Mendelian randomization estimates for the association between anti-cytomegalovirus IgG levels and risk of 9 cardiovascular diseases. DVT, deep vein thrombosis; OR, odds ratio.
See this image and copyright information in PMC

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