Evidence map›Paper›PMID 42350845›Full record

ArticleFunctional & integrative genomics2026

Integrative genetic analysis reveals shared genetic architecture underlying coronary artery disease, CT-Defined coronary atherosclerosis, and cardiometabolic risk factors.

Yao Zhao, Yingying Xie, Didi Wen, Jin Zhang, Ziliang Xu, Zhibin Wu, Jiaming Li, Yuanqiang Zhu, Minwen Zheng

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Article in Functional & integrative genomics, 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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5 · Who and what money

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9 authors.

Yao Zhao *Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Yingying Xie *Department of Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China.
Didi WenDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Jin ZhangDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Ziliang XuDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Zhibin WuDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Jiaming LiDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Yuanqiang ZhuDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. zhu_yq_fmmu@163.com.
Minwen ZhengDepartment of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. zhengmw2007@163.com.

Funding

National Natural Science Foundation of China 82572213
6 · The paper itself

Abstract

Coronary artery disease (CAD), computed tomography-defined coronary atherosclerosis (CT-CA), and cardiometabolic risk factors (CMRFs) are epidemiologically intertwined, yet their shared genetic basis has been explored through pairwise analyses. A comprehensive framework integrating clinical disease, subclinical imaging phenotypes, and upstream risk factors simultaneously remains lacking. We integrated large-scale genome-wide association study summary statistics for CAD, two CT-CA phenotypes (coronary artery calcium score and segment involvement score), and seven major CMRFs. Using MiXeR, we quantified global polygenic overlap, followed by cross-phenotype Bayesian analysis to identify pleiotropic variants. We observed substantial polygenic sharing across traits. A total of 530 shared SNPs were identified across 14 trait groups, yielding 325 unique lead pleiotropic variants. These loci were enriched in lipid metabolism and extracellular matrix organization pathways. Colocalization analysis in coronary artery tissue revealed 61 loci with shared causal variants influencing gene expression, including established cardiovascular genes such as PHACTR1 and ADAMTS7. Protein-protein interaction analysis identified lipid-related hub genes (e.g., APOE, PCSK9, LPL), most of which are druggable. Local genetic correlation analyses independently validated shared effects at 51 loci. Collectively, our findings demonstrate extensive shared genetic architecture linking cardiometabolic dysregulation, subclinical coronary atherosclerosis, and clinical CAD, providing insights into shared genetic mechanisms and a foundation for genetically informed risk stratification and precision prevention strategies.

Indexed as

Cardiometabolic Risk FactorsCoronary Artery DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMicrofilament ProteinsPolymorphism, Single NucleotideTomography, X-Ray ComputedMicrofilament ProteinsPHACTR1 protein, humanCardiometabolic risk factorsComputed tomography imagingCoronary artery diseaseCoronary atherosclerosisGenetic pleiotropyGenome-wide association studies

Identifiers

PMID42350845

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