Evidence mapPaperPMID 42427177Full record

ArticleClinical and translational medicine2026

Precision medicine for atherosclerotic cardiovascular disease: Integrative genomics maps risk loci and AI-predicted functional consequences.

Liwan Fu, Xiaodi Han, Qin Liu, Yuquan Wang, Yue-Qing Hu

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Liwan FuCenter for Non-Communicable Disease Management, Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.ORCID 0000-0002-7851-6379
Xiaodi HanCenter for Non-Communicable Disease Management, Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Qin LiuDepartment of Ultrasound, Capital Center for Children's Health, Capital Medical University, Beijing, China.
Yuquan WangState Key Laboratory of Genetic Engineering, Human Phenome Institute, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, China.
Yue-Qing HuState Key Laboratory of Genetic Engineering, Human Phenome Institute, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, China.ORCID 0000-0001-9151-7619

Funding

Beijing Chronic Disease Prevention and Health Education Research Association and Zhongguancun Talent Association's 'Future Talents' Training Program in the Medical Engineering Field MBRC0012025055Capital's Funds for Health Improvement and Research 2024-4-20911National Key R&D Program of China 2023YFF1205101National Natural Science Foundation of China 82204063Young Elite Scientists Sponsorship Program of the Beijing High Innovation Plan 20250685
6 · The paper itself

Abstract

backgroundAtherosclerotic cardiovascular disease (ASCVD) is a leading cause of global morbidity and mortality, but its genetic architecture remains incompletely understood. This study aims to uncover novel genetic insights into ASCVD through multivariate genomic analysis and molecular structure predictions.

methodsWe analysed genomic data from over 3.8 million individuals across various ASCVD phenotypes, including coronary heart disease, stroke, transient ischemic attack, peripheral artery disease and abdominal aortic aneurysm. Advanced tools such as Genomic Structural Equation Modeling, fine-mapping, FUSION, FOCUS and other functional annotation methods were applied to identify causal single nucleotide polymorphisms associated with ASCVD. Protein structural analysis was performed using AlphaFold3, and AI-driven thermodynamic analysis (ThermoMPNN) assessed the stability and functional consequences of mutations.

resultsOur analysis revealed 347 genome-wide significant variants linked to ASCVD, distributed across 213 loci. Ninety of these variants were not identified in any of the five input GWAS datasets. Upon cross‑referencing with large‑scale external GWAS, 19 of the 90 variants showed no prior association with any cardiovascular or metabolic trait, 15 were previously reported only in risk factor GWAS, and 56 had been reported in direct ASCVD endpoint GWAS. The latter group includes the DCLRE1B rs11552449 missense mutation. Nevertheless, AI‑based structural and thermodynamic analyses revealed that this mutation (H61Y) disrupts DCLRE1B protein stability, increases conformational flexibility, and alters solvent‑accessible surface area-mechanistic insights that have not been previously described.

conclusionsThis study provides a hypothesis‑generating genetic landscape of ASCVD, unveiling novel variants and their molecular impacts. These findings enhance our understanding of ASCVD mechanisms and may offer potential avenues pending experimental validation and targeted therapies in cardiovascular disease.

Indexed as

AtherosclerosisGenomicsPrecision MedicineGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideAI predictionASCVDDCLRE1Bgenomic SEMrs11552449

Identifiers

PMID42427177
PMCPMC13351343

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.