The Causal Relationships between Lipids related Traits and Atrial Fibrillation/Flutter: Two-sample Mendelian Randomization Analysis

Background: Atrial fibrillation (AF) stands as the most prevalent form of sustained arrhythmia, but the relationship between lipid is unclear. Objective: The objective of this research is to examine the causal relationships between 249 blood lipid-related traits and the likelihood of developing AF and atrial flutter by utilizing two-sample Mendelian randomization (MR) method. Methods: Data on the single nucleotide polymorphisms (SNPs) related to lipid-related traits were obtained from a proof-of-concept cross-platform Genome-wide association study GWAS datasets including participants ranging from 110,051 to 115,082 from the UK Biobank study, and data for AF were from the meta-analysis of GWASs and FinnGen study. The univariable and multivariable MR analysis were conducted to explore whether genetic evidence of individual lipid-related traits was significantly associated with AF risks. Results: We identified thirty lipid traits that exhibit a significant correlation with AF, in addition to 17 traits linked to AF and atrial flutter. Very-low-density lipoprotein (VLDL) and particle diameters were associated with AF (OR: 0.93, 95%CI 0.88-0.98, p=0.0055). A high percentage of triglycerides in VLDL is a protective factor for AF, whereas an elevated percentage of cholesterol, cholesteryl esters, free cholesterol, and phospholipids are risk factors for AF. Additionally, higher concentrations of intermediate-density lipoprotein (IDL) particles and elevated phospholipid levels in IDL were identified as risk factors for AF (OR: 1.06, 95%CI 1.0-1.13, p=0.0497 for particles; OR: 1.06, 95%CI 1.0-1,12, p=0.0404 for phospholipids). Notably, a higher percentage of monounsaturated fatty acids was found to be protective against AF (OR: 0.94, 95%CI 0.88-0.99, p=0.0258). Conclusion: our study identified certain lipid-relates traits are associated with AF/atrial flutter. Future research should focus on the underlying biological mechanisms and the role of lipid modulation to further inform AF prevention strategies.