Plasma Phospholipid Fatty Acids and Risk of Atrial Fibrillation: A Mendelian Randomization Study

Available evidence on the associations of dietary and circulating levels of long-chain n-3 fatty acids, which have potential antiarrhythmic properties, and other fatty acids with atrial fibrillation is conflicting and limited. We conducted a Mendelian randomization study to assess the associations between plasma phospholipid fatty acid levels and atrial fibrillation. Summary-level data of atrial fibrillation were available from 65,446 cases and 522,744 non-cases included in the Atrial Fibrillation Consortium. Sixteen single-nucleotide polymorphisms associated with ten fatty acids at significance level of p < 5 × 10^-8 were identified as instrumental variables from the hitherto largest genome-wide association studies for plasma fatty acids. The fixed-effects inverse-variance weighted method was used to assess the association of individual plasma fatty acids and atrial fibrillation risk. The random-effects inverse-variance weighted method, weighted median method, and Mendelian randomization (MR)-Egger method were employed as the sensitivity analyses. Genetic predisposition to higher levels of any of the ten individual fatty acids was not associated with atrial fibrillation risk.