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. 2024 Jun 14;14(1):13733.
doi: 10.1038/s41598-024-64789-9.

Assessing the causal relationship between circulating immune cells and abdominal aortic aneurysm by bi-directional Mendelian randomization analysis

Weiqiang Ruan  1 , Xiaoqin Zhou  2   3   4 , Ting Wang  4 , Huizhen Liu  4 , Guiying Zhang  3 , Jiaoyan Sun  5 , Ke Lin  6
Affiliations

Assessing the causal relationship between circulating immune cells and abdominal aortic aneurysm by bi-directional Mendelian randomization analysis

Weiqiang Ruan et al. Sci Rep. .

Abstract

Although there is an association between abdominal aortic aneurysm (AAA) and circulating immune cell phenotypes, the exact causal relationship remains unclear. This study aimed to explore the causal relationships between immune cell phenotypes and AAA risk using a bidirectional two-sample Mendelian randomization approach. Data from genome-wide association studies pertaining to 731 immune cell traits and AAA were systematically analyzed. Using strict selection criteria, we identified 339 immune traits that are associated with at least 3 single nucleotide polymorphisms. A comprehensive MR analysis was conducted using several methods including Inverse Variance Weighted, Weighted Median Estimator, MR-Egger regression, Weighted Mode, and Simple Median methods. CD24 on switched memory cells (OR = 0.922, 95% CI 0.914-0.929, P = 2.62e-79) at the median fluorescence intensities level, and SSC-A on HLA-DR + natural killer cells (OR = 0.873, 95% CI 0.861-0.885, P = 8.96e-81) at the morphological parameter level, exhibited the strongest causal associations with AAA. In the reverse analysis, no significant causal effects of AAA on immune traits were found. The study elucidates the causal involvement of multiple circulating immune cell phenotypes in AAA development, signifying their potential as diagnostic markers or therapeutic targets. These identified immune traits may be crucial in modulating AAA-related inflammatory pathways.

Keywords: Abdominal aortic aneurysm; Genome-wide association study; Immune cells; Mendelian randomization.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Schematic Representation of the Mendelian Randomization (MR) Analysis. The flowchart of the study based on three assumptions: (1) the instrumental variables (IVs) selected from datasets were associated with exposure; (2) the IVs were not associated with confounders; and (3) the IVs influences the outcome only through exposure. AAA, Abdominal Aortic Aneurysm, SNP single nucleotide polymorphism.
Figure 2
Figure 2
Causal Effects of immunophenotypes on Abdominal Aortic Aneurysm. IVW inverse variance weighted, WMe weighted median, MFI median fluorescence intensitie.
Figure 3
Figure 3
Scatter plots of the effect of the immunophenotypes on Abdominal Aortic Aneurysm.
Figure 4
Figure 4
Leave-one-out plots of the effect of immunophenotypes on Abdominal Aortic Aneurysm.
See this image and copyright information in PMC

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