Evidence map›Paper›PMID 42902308›Full record

ArticleDiabetology & metabolic syndrome2026

GlycA-gene interactions in cardiovascular-kidney-metabolic syndrome: evidence from genetic association.

Mingyang Yuan, Suwen Cao, Xing Wan, Yuting Yang, Siyu Fan, Jiang Xie, Han Wang

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Article in Diabetology & metabolic syndrome, 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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7 authors.

Mingyang YuanDepartment of Pediatrics, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.ORCID http://orcid.org/0009-0006-7187-3687
Suwen CaoDepartment of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China, Sichuan, 646099.
Xing WanDepartment of Pediatrics, The Third People's Hospital of Chengdu, Chengdu, 610031, Sichuan, China.
Yuting YangDepartment of Pediatrics, The Third People's Hospital of Chengdu, Chengdu, 610031, Sichuan, China.
Siyu FanDepartment of General Practice, The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, Heilongjiang, China.
Jiang XieDepartment of Pediatrics, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China. xiejiang@swjtu.edu.cn.
Han WangDepartment of Cardiology, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China. wanghan@swjtu.edu.cn.ORCID http://orcid.org/0000-0002-1123-4086

Funding

Sichuan Province Science and Technology Support Program (CN) 2024YFHZ0080Supported by National Natural Science Foundation of China U23A20335The Third People's Hospital of Chengdu Foundation CSY-YN-03-2024-023
6 · The paper itself

Abstract

objectiveCardiovascular-Kidney-metabolic (CKM) syndrome is a concept introduced by the American Heart Association, describing systemic diseases resulting from the pathophysiological interaction among obesity, stroke, type 2 diabetes, chronic kidney disease, and cardiovascular disease. Glycoprotein acetyls (GlycA) is a novel biomarker for systemic inflammation and cardiovascular risk. This study aims to uncover the shared genetic architecture between GlycA and CKM, identify common risk loci and key tissues, and clarify the mechanisms linking these conditions.

methodsUsing summary data from large-scale GWAS studies, we evaluated both global and local genetic correlations between GlycA and various components of CKM. A cross-trait pleiotropic analysis was conducted to identify shared pleiotropic loci and related genes. FUSION was used to find susceptibility genes linked to GlycA and CKM. A comprehensive set of functional annotations and tissue-specific analyses was performed to uncover potential connections between these traits. Furthermore, a multi-trait colocalization method was utilized to explore the underlying mechanisms of the association between GlycA and CKM.

resultsOur study revealed a close genetic correlation between GlycA and CKM. We identified 260 potential SNPs that were corrected using the Bonferroni method, of which 30 passed the colocalization test (PP.H4 > 0.70). Notably, locus 9q34.2 appeared in both GlycA-T2D and GlycA-HF trait pairs. By integrating post-GWAS methods, we identified 53 potentially drug targets (CMIP, DNAJC5G, FCGRT, etc.). FUSION analysis identified 23 shared susceptibility genes for GlycA and CKM (ZPR1, IL6R, PABPC4, etc.). Analysis of tissue enrichment at the SNP level revealed pleiotropic mechanisms associated with whole blood and liver. Gene-level analysis highlighted important roles of metabolic signaling pathways. Furthermore, multi-trait colocalization analysis suggested that rs1260326 and rs2925979 may play significant roles in the mechanistic link between GlycA and CKM.

conclusionOur study confirmed a significant genetic association and shared genetic structure between GlycA and CKM, revealing potential mechanisms that may be involved.

Indexed as

Cardiovascular-Kidney-Metabolic SyndromeCross-trait pleiotropy analysisGenetic correlationGenome-wide association studiesGlycoprotein acetyls

Identifiers

PMID42902308
PMCPMC13685344

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