Evidence map›Paper›PMID 42784636›Full record

ArticlePloS one2026

Shared genetic architecture of HCM and AF: Elevated NPPA/ANP is linked to atrial electrical remodeling.

A Z M Fahim Siddique, Xinru Wang, Ruyi Du, Yuchen Wang, Qi Wang, Yuanyuan Guo, Tiankai Li

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Article in PloS one, 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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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

A Z M Fahim SiddiqueDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.ORCID https://orcid.org/0009-0001-0702-8861
Xinru WangDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Ruyi DuDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Yuchen WangDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Qi WangDepartment of Cardiology, Beidahuang Industry Group General Hospital, Harbin, China.
Yuanyuan GuoDepartment of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Tiankai LiDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.ORCID https://orcid.org/0000-0003-1997-9549

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypertrophic cardiomyopathy (HCM) patients exhibit heightened susceptibility to atrial fibrillation (AF), yet the underlying genetic nexus remains poorly defined. This study aimed to identify genes common to HCM and AF, thereby revealing the underlying pathogenesis of susceptibility to AF in HCM patients.

methodsGenes associated with HCM and AF were sourced from the Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD), GeneCards, and DisGeNET databases. We conducted a comparative analysis to identify overlapping genes between HCM and AF for further investigation, which included functional enrichment analysis, protein-protein interaction networks, and immune infiltration assessment. Key hub genes were determined using cytoHubba, a Cytoscape plugin, and their validation was performed using independent datasets GSE36961 and GSE115574. The genes corroborated by these datasets were additionally validated in clinical samples.

resultsA total of 11 overlapping genes were identified between HCM and AF. Functional enrichment and immune infiltration analyses revealed their involvement in immune regulation and inflammatory processes. Three hub genes NPPA, ACE, and POMC were recognized as key molecular links between HCM and AF. Validation using the GSE36961 dataset confirmed the upregulation of NPPA in HCM, supporting its potential as a central gene connecting the two conditions. Consistent with the bioinformatics findings, exploratory clinical verification findings of serum levels of N-terminal fragment of A-type natriuretic peptide (NT-proANP), encoded by NPPA, were markedly elevated in both the HCM and HCM with AF groups compared with healthy controls (P < 0.01). Moreover, NT-proANP concentrations were significantly higher in the HCM + AF group than in the HCM-only group (P < 0.01).

conclusionThis study identifies a shared genetic link between HCM and AF. The findings strongly associate elevated NT-proANP levels, encoded by the NPPA gene, with AF in HCM patients. We propose NT-proANP as a promising circulating biomarker for stratifying AF risk in this patient population.

Indexed as

Atrial FibrillationAtrial Natriuretic FactorAtrial RemodelingCardiomyopathy, HypertrophicGenetic Predisposition to DiseaseHumansProtein Interaction MapsAtrial Natriuretic FactorNPPA protein, human

Identifiers

PMID42784636
PMCPMC13606995

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