A causal relationship between appendicular lean mass and atrial fibrillation: A two sample Mendelian randomization study

Background and aim: The relationship between appendicular lean mass (ALM) and most cardiovascular events has been established, but the direct association between ALM and atrial fibrillation (AF) remains uncertain. Methods and results: Herein, we identified 494 single-nucleotide polymorphisms (SNPs) strongly associated with ALM as instrumental variables (P < 5E-8) based on a genome-wide association study (GWAS) with 450,243 European participants. Then, we employed five Mendelian randomization (MR) analysis methods to investigate the causal relationship between ALM and AF. All results indicated a causal relationship between ALM and AF, among Inverse variance weighted (P = 8.44E-15, odds ratio [OR]: 1.16, 95 % confidence interval [CI]: 1.114-1.198). Furthermore, we performed a sensitivity analysis, which revealed no evidence of pleiotropy (egger_intercept = 0.000089, P = 0.965) or heterogeneity (MR Egger, Q Value = 0.980; Inverse variance weighted, Q Value = 0.927). The leave-one-out method demonstrates that individual SNPs have no driven impact on the whole causal relationship. Multivariable MR analysis indicates that, after excluding the influence of hypertension and coronary heart disease, a causal relationship between ALM and AF still exists (P = 7.74E-40, OR 95 %CI: 1.389 (1.323-1.458)). Importantly, the Radial MR framework analysis and Robust Adjusted Profile Score (RAPS) further exhibit the robustness of this causal relationship. Conclusion: A strong association between ALM and AF was confirmed, and high ALM is a risk factor for AF. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).