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Updated: Jul 2, 2025
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Published on: July 20, 2022
A causal relationship between appendicular lean mass and atrial fibrillation: A two sample Mendelian randomization
Yongfei Song1, Zequn Zheng2, Jiale Hu3
1Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo Medical Center Lihuili Hospital, Ningbo University, No. 378 Dongqing Road, Yinzhou District, Ningbo, Zhejiang, 315000, China; Department of Cardiology, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315040, China.
High appendicular lean mass (ALM) is a significant risk factor for developing atrial fibrillation (AF). This study confirms a causal link, suggesting ALM influences AF development.
Area of Science:
- Genetics and Cardiovascular Health
Background:
- The link between appendicular lean mass (ALM) and cardiovascular health is known, but its specific association with atrial fibrillation (AF) is unclear.
- Understanding this relationship is crucial for predicting and preventing AF.
Purpose of the Study:
- To investigate the potential causal relationship between appendicular lean mass (ALM) and atrial fibrillation (AF) using genetic data.
- To determine if higher ALM is a risk factor for developing AF.
Main Methods:
- Utilized a large genome-wide association study (GWAS) dataset of 450,243 European participants to identify single-nucleotide polymorphisms (SNPs) associated with ALM.
- Employed multiple Mendelian randomization (MR) methods, including Inverse Variance Weighted (IVW) and Robust Adjusted Profile Score (RAPS), to assess causality.
- Conducted sensitivity analyses to test for pleiotropy and heterogeneity, and performed multivariable MR to adjust for confounding factors like hypertension and coronary heart disease.
Main Results:
- Identified 494 SNPs strongly associated with ALM.
- All MR analyses consistently indicated a causal relationship between higher ALM and an increased risk of AF (e.g., IVW: OR 1.16, P=8.44E-15).
- Sensitivity analyses showed no significant pleiotropy or heterogeneity, and multivariable MR confirmed the independent causal effect of ALM on AF (OR 1.389, P=7.74E-40).
Conclusions:
- Confirmed a strong causal association between appendicular lean mass (ALM) and atrial fibrillation (AF).
- High ALM is identified as a significant risk factor for developing AF.
