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Updated: Jun 20, 2025
Porcine Model of Infrarenal Abdominal Aortic Aneurysm
Published on: November 21, 2019
Circulating inflammatory proteins and abdominal aortic aneurysm: A two-sample Mendelian randomization and
Zhan Chen1, Tingting Chen2, Ruimin Lin1
1Department of Vascular Surgery, Beijing Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.
Objectives:
Inflammatory proteins are implicated in the progression of abdominal aortic aneurysms (AAA); however, it remains debated whether they are causal or consequential. This study aimed to assess the influence of circulating inflammatory proteins on AAA via two-sample Mendelian randomization (MR) and colocalization analysis.
Methods:
Summary data on 91 circulating inflammatory protein levels were extracted from a comprehensive protein quantitative trait loci (pQTL) study involving 14,824 individuals. Genetic associations with AAA were derived from the FinnGen study (3,869 cases and 381,977 controls). MR analysis was conducted to assess the relationships between proteins and AAA risk. Colocalization analysis was employed to explore potential shared causal variants between identified proteins and AAA.
Results:
Using a two-sample bidirectional MR study, our findings suggested that genetically predicted elevated levels of TGFB1 (OR = 1.21, P = 0.003), SIRT2 (OR = 1.196, P = 0.031) and TNFSF14 (OR = 1.129, P = 0.034) were linked to an increased risk of AAA. Conversely, genetically predicted higher levels of CD40 (OR = 0.912, P = 0.049), IL2RB (OR = 0.839, P = 0.028) and KITLG (OR = 0.827, P = 0.008) were associated with a decreased risk of AAA. Colocalization analyses supported the association of TGFB1 and SIRT2 levels with AAA risk.
Conclusions:
The proteome-wide MR and colocalization study identified TGFB1 and SIRT2 as being associated with the risk of AAA, warranting further investigation as potential therapeutic targets.
Insights
This study investigated the link between inflammatory proteins and abdominal aortic aneurysms (AAA). Findings suggest TGFB1 and SIRT2 may increase AAA risk, highlighting potential therapeutic targets.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Research
- Proteomics
Background:
- Inflammatory proteins are linked to abdominal aortic aneurysm (AAA) progression, but their causal role is unclear.
- Understanding the relationship between specific circulating proteins and AAA pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the causal influence of circulating inflammatory proteins on the risk of abdominal aortic aneurysms (AAA).
- To utilize two-sample Mendelian randomization (MR) and colocalization analysis to assess protein-AAA associations.
Main Methods:
- Extracted summary data for 91 circulating inflammatory proteins from a protein quantitative trait loci (pQTL) study (14,824 individuals).
- Utilized genetic association data for AAA from the FinnGen study (3,869 cases, 381,977 controls).
- Performed two-sample Mendelian randomization and colocalization analyses to identify causal relationships and shared variants.
Main Results:
- Genetically predicted higher levels of TGFB1, SIRT2, and TNFSF14 were associated with increased AAA risk.
- Genetically predicted higher levels of CD40, IL2RB, and KITLG were associated with decreased AAA risk.
- Colocalization analysis supported the association of TGFB1 and SIRT2 with AAA risk.
Conclusions:
- TGFB1 and SIRT2 are identified as circulating proteins significantly associated with AAA risk.
- These proteins represent potential therapeutic targets for abdominal aortic aneurysms, meriting further investigation.
