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Related Experiment Video

Updated: Jan 24, 2026

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Causal Impact of Genetically Predicted Leptin Levels on Atrial Fibrillation Risk: Evidence from Bidirectional

Xiaoyong Huang1,2, Fuyuan Li1,2, Yun Zhang3

  • 1Department of Cardiology, Lishui People's Hospital, the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.

Endocrine, Metabolic & Immune Disorders Drug Targets
|January 23, 2026
PubMed
Summary

Elevated leptin levels causally increase the risk of atrial fibrillation (AF), independent of body fat. This finding suggests leptin may be a key biomarker for AF susceptibility.

Keywords:
Mendelian randomizationatrial fibrillationcausal inferencegenome-wide association study (GWAS)leptinsingle nucleotide polymorphisms (SNPs).

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Area of Science:

  • Cardiology
  • Genetics
  • Metabolic Research

Background:

  • Atrial fibrillation (AF) is a common arrhythmia with significant health impacts.
  • The link between obesity-related adipokines like leptin and AF is unclear regarding causality.

Purpose of the Study:

  • To investigate the causal relationship between genetically predicted leptin levels and AF risk using Mendelian randomization.
  • To determine if leptin influences AF independently of adiposity.

Main Methods:

  • Utilized a bidirectional two-sample Mendelian randomization (MR) framework.
  • Employed genetic instruments for leptin from GWAS and AF data from large meta-analyses.
  • Applied IVW, weighted median, and MR-RAPS methods with sensitivity analyses.

Main Results:

  • Genetically predicted higher leptin levels were significantly associated with increased AF risk (OR=1.18).
  • Reverse MR analysis showed no causal effect of AF on leptin levels.
  • Sensitivity analyses confirmed the robustness of these findings.

Conclusions:

  • This study provides strong genetic evidence for a unidirectional causal link between elevated leptin and AF risk.
  • Leptin may serve as a potential biomarker for AF susceptibility, warranting further research into its role in atrial remodeling and therapeutic potential.