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Peer-reviewedCC BY-NC-NDJournal of cardiothoracic surgery

Circulating 16 micronutrients concentration and risk of abdominal aortic aneurysm: a two-sample mediation Mendelian randomization analysis.

  • Wenpeng Zhao1,2
  • Yiliang Hu1
  • Xiya Yan3
  • Zhihan You3
  • Weimin Zhou4
  • Shichen Liu5
5 affiliations
  1. 1Department of Vascular Surgery, Jiangxi Medical College, The Second Affiliated Hospital of Nanchang University, Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, China.
  2. 2Department of Vascular Surgery, The First People's Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
  3. 3Queen Mary College of Nanchang University, Xuefu Road, Nanchang, Jiangxi, China.
  4. 4Department of Vascular Surgery, Jiangxi Medical College, The Second Affiliated Hospital of Nanchang University, Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, China. [email protected].
  5. 5Department of Vascular Surgery, Jiangxi Medical College, The Second Affiliated Hospital of Nanchang University, Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, China. [email protected].
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Abstract

Background

Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease involving various genetic and metabolic factors. Micronutrients play critical roles in cardiovascular health, yet their specific impacts on AAA remain unclear. This study aims to explore the effects of micronutrients calcium and zinc on AAA risk mediated by plasma proteins using the two-sample Mendelian Randomization (MR) approach.Methods

Utilizing large-scale GWAS data from the UK Biobank; FinnGen databases and Decode database, we assessed the causal relationships between 16 micronutrients concentration and AAA risk and analyzed potential mechanisms mediated by plasma proteins. Strict statistical methods were used to select genetic instrumental variables, and multivariable MR analyses were conducted to dissect direct and indirect effects.Results

Genetically predicted calcium and zinc levels showed nominally significant associations with AAA risk (IVW Ca: OR 2.32, 95% CI 1.04-5.18, p = 0.04; IVW Zn: OR 1.24, 95% CI 1.05-1.47, p = 0.01). Proteome-wide MR analyses identified several AAA-associated plasma proteins. Among the zinc-related analyses, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2) was identified as a partial and preliminary mediating factor for the zinc-AAA association. The mediation analysis suggested a modest mediated proportion through ITIH2 (4.65%, 95% CI 0.701%-8.59%). These findings should be interpreted cautiously because the zinc analysis was based on two instrumental variables and the primary micronutrient screen was exploratory.Conclusions

This study provides suggestive genetic evidence that calcium and zinc may be associated with AAA risk. In addition, ITIH2 may act as a partial and preliminary mediator of the zinc-AAA association, although the mediated proportion was modest and the evidence requires validation in larger datasets. These results highlight the need for further investigation of micronutrients, plasma proteins, and AAA biology before clinical translation.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026circulating,
  title = {{Circulating 16 micronutrients concentration and risk of abdominal aortic aneurysm: a two-sample mediation Mendelian randomization analysis.}},
  author = {Wenpeng Zhao and Yiliang Hu and Xiya Yan and Zhihan You and Weimin Zhou and Shichen Liu},
  journal = {Journal of cardiothoracic surgery},
  year = {2026},
  month = jul,
  doi = {10.1186/s13019-026-04593-w},
  url = {https://europepmc.org/article/MED/42907923},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Circulating 16 micronutrients concentration and risk of abdominal aortic aneurysm: a two-sample mediation Mendelian randomization analysis.
AU  - Wenpeng Zhao
AU  - Yiliang Hu
AU  - Xiya Yan
AU  - Zhihan You
AU  - Weimin Zhou
AU  - Shichen Liu
PY  - 2026
DA  - 2026/07/01
JO  - Journal of cardiothoracic surgery
DO  - 10.1186/s13019-026-04593-w
UR  - https://europepmc.org/article/MED/42907923
AB  - Background  Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease involving various genetic and metabolic factors. Micronutrients play critical roles in cardiovascular health, yet their specific impacts on AAA remain unclear. This study aims to explore the effects of micronutrients calcium and zinc on AAA risk mediated by plasma proteins using the two-sample Mendelian Randomization (MR) approach.Methods  Utilizing large-scale GWAS data from the UK Biobank; FinnGen databases and Decode database, we assessed the causal relationships between 16 micronutrients concentration and AAA risk and analyzed potential mechanisms mediated by plasma proteins. Strict statistical methods were used to select genetic instrumental variables, and multivariable MR analyses were conducted to dissect direct and indirect effects.Results  Genetically predicted calcium and zinc levels showed nominally significant associations with AAA risk (IVW Ca: OR 2.32, 95% CI 1.04-5.18, p = 0.04; IVW Zn: OR 1.24, 95% CI 1.05-1.47, p = 0.01). Proteome-wide MR analyses identified several AAA-associated plasma proteins. Among the zinc-related analyses, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2) was identified as a partial and preliminary mediating factor for the zinc-AAA association. The mediation analysis suggested a modest mediated proportion through ITIH2 (4.65%, 95% CI 0.701%-8.59%). These findings should be interpreted cautiously because the zinc analysis was based on two instrumental variables and the primary micronutrient screen was exploratory.Conclusions  This study provides suggestive genetic evidence that calcium and zinc may be associated with AAA risk. In addition, ITIH2 may act as a partial and preliminary mediator of the zinc-AAA association, although the mediated proportion was modest and the evidence requires validation in larger datasets. These results highlight the need for further investigation of micronutrients, plasma proteins, and AAA biology before clinical translation.
SN  - 1749-8090
ER  -