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Updated: Jan 7, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

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Genetic predisposition and mediating pathways in ischemic stroke-induced cardiac arrhythmias: a genome-wide analysis

Wei Zhao1, Hong-Bin Lin1, Meng Li1

  • 1Department of Anesthesiology, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Institute of Perioperative Medicine and Organ Protection, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Journal of Advanced Research
|December 29, 2025
PubMed

Insights

This study establishes a causal link between ischemic stroke and cardiac arrhythmias, identifying diabetic complications as a key mediator. A shared genetic variant in the PDE3A gene and the cAMP pathway are implicated in stroke-heart syndrome.

Area of Science:

  • Cardiovascular Research
  • Neurology
  • Genetics

Background:

  • Stroke-heart syndrome (SHS) involves complex interactions between the nervous and cardiovascular systems.
  • Cardiac arrhythmia is a common complication in SHS, but the causal relationship with ischemic stroke remains unclear.

Purpose of the Study:

  • To investigate the causal role of ischemic stroke in cardiac complications.
  • To identify shared genetic pathways and potential mediators between ischemic stroke and cardiac arrhythmias.

Main Methods:

  • Mendelian randomization and genome-wide association studies were employed.
  • Mediation, colocalization, Gene Ontology, and KEGG pathway analyses were conducted.
  • Validation utilized Gene Expression Omnibus (GEO) data for atrial fibrillation.

Main Results:

  • A significant correlation was found between arrhythmias (ventricular tachyarrhythmias, atrial fibrillation) and ischemic stroke.
  • Diabetic complications significantly mediated the effect of ischemic stroke on cardiac arrhythmias.
  • A shared causal variant (rs11045239) in the PDE3A gene and the cAMP signaling pathway were identified, with PDE3A upregulated in atrial fibrillation.

Conclusions:

  • A causal link between ischemic stroke and cardiac arrhythmias, mediated by diabetic complications, was demonstrated.
  • The identified PDE3A gene variant and cAMP pathway offer potential targets for predicting and managing SHS.
Abstract

Keywords:
Cardiac arrhythmiasDiabetic complicationsIschemic strokeMendelian randomizationPDE3A gene

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