ArticleArteriosclerosis, thrombosis, and vascular biology2025
Circulating Protein Mediators Linking Genetically Predicted Smoking to Abdominal Aortic Aneurysm: A Genomic-Proteomic Analysis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Systolic blood pressure variability as a risk factor for abdominal aortic aneurysm: a prospective cohort study with genomic and proteomic profiling.European journal of epidemiology · 2026Article
- Cross-Omics Identification and Validation of PCSK9 as a Candidate Molecule Associated with Aortic Dissection and Negative Remodeling After TEVAR.Journal of cardiovascular development and disease · 2026Article
- A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study.Journal of the National Cancer Institute · 2026Article
- Epigenetics in Abdominal Aortic Aneurysm: Mechanisms and Risk Prediction.medRxiv : the preprint server for health sciences · 2026Article
- Circulating proteins as key genetically proxied mediators in the pathway from smoking to intracranial aneurysm disease: A mediation Mendelian randomization analysis.Tobacco induced diseases · 2026Article
- A sparse proteomic risk score incorporating plasma MMP12 level improves prediction of abdominal aortic aneurysm.medRxiv : the preprint server for health sciences · 2025Article
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8 authors.
Funding
Abstract
backgroundSmoking is a well-established risk factor for abdominal aortic aneurysm (AAA). However, the molecular pathways underlying this relationship remain poorly understood. This study aimed to identify circulating protein mediators that may explain the association between smoking and AAA.
methodsWe conducted a network Mendelian randomization study using summary-level data from the largest available genome-wide association studies. Our primary smoking exposure was the lifetime smoking index, with smoking initiation and cigarettes per day included as supplementary traits. The AAA data set comprised 39 221 cases and 1 086 107 controls. Protein data were sourced from 2 large cohorts: UKB-PPP (the UK Biobank Pharma Proteomics Project), where proteins were measured using the Olink platform in 54 219 individuals, and deCODE, where proteins were measured using the SomaScan platform in 35 559 individuals. Two-sample Mendelian randomization was used to estimate the association between smoking and AAA (β
resultsGenetically proxied smoking traits were consistently associated with an increased risk of AAA. The lifetime smoking index was associated with the levels of 543 out of 5764 unique circulating proteins, with 470 of these associations replicated in supplementary analyses using additional smoking traits and protein sources. Among the smoking-related proteins, genetically proxied levels of 22 were associated with AAA risk. Eight mediation pathways were identified, with ADAMTS15 (a disintegrin and metalloproteinase with thrombospondin motifs 15), IL1RN (interleukin-1 receptor antagonist protein), MMP12 (matrix metalloproteinases 12), PGF (placental growth factor), PCSK9 (proprotein convertase subtilisin/kexin type 9), and UXS1 (UDP-glucuronic acid decarboxylase 1) representing key mediators.
conclusionsThis study identified numerous circulating proteins that are potentially causally linked to smoking, and 8 of these proteins were found to mediate the association between smoking and AAA risk.
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