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We performed univariable and multivariable Mendelian randomization (MR) analysis to evaluate the association between blood lipids and risk of atrial fibrillation (AF), including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), Apolipoprotein A1, and Apolipoprotein B. Methods: Data on the single nucleotide polymorphisms (SNPs) related to blood lipids were obtained from the UK Biobank study with more than 300,000 subjects of White British European ancestry, and data for AF were from the latest meta-analysis of Genome-wide association study (GWASs) with six independent cohorts with more than 1,000,000 subjects of European ancestry. The univariable MR analysis was conducted to explore whether genetic evidence of individual lipid-related traits was significantly associated with AF risks and multivariable MR analysis with three models was performed to assess the independent effects of lipid-related traits. Results: The IVW estimate showed that genetically predicted LDL-C (OR: 1.016, 95% CI: 0.962–1.073, p = 0.560), HDL-C (OR: 0.951, 95% CI: 0.895–1.010, p = 0.102), TG (OR: 0.961, 95% CI: 0.889–1.038, p = 0.313), Apolipoprotein A1 (OR: 0.978, 95% CI: 0.933–1.025, p = 0.356), and Apolipoprotein B (OR: 1.008, 95% CI: 0.959–1.070, p = 0.794) were not causally associated with the risk of AF. Sample mode (OR: 0.852, 95% CI: 0.731–0.993, p = 0.043) and weighted mode (OR: 0.907, 95% CI: 0.841–0.979, p = 0.013) showed that a 1-unit increase in TG (mmol/L) was causally associated with a 14.8% and 9.3% relative decrease in AF risk, respectively. The multivariable MR analysis with model 1, 2, and 3 indicated that TG, LDL-C, HDL-C, Apolipoprotein A1, and Apolipoprotein B were not associated with the lower risk for AF. Conclusions: Our multivariable Mendelian randomization analysis (MVMR) finding suggested no genetic evidence of lipid traits was significantly associated with AF risk. Furthermore, more work is warranted to confirm the potential association between lipid traits and AF risks.

The Relationship between Blood Lipids and Risk of Atrial Fibrillation: Univariable and Multivariable Mendelian Randomization Analysis