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

Abstract

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.

Roles for circulating polyunsaturated fatty acids in ischemic stroke and modifiable factors: a Mendelian randomization study

“…Thus, the effects of PUFA on IS risk still left vague. Furthermore, there was an amount of design applying Mendelian randomization (MR) to access the effect of one or part composition of PUFA on coronary heart disease or other cardiovascular diseases [30][31][32], but no analogous MR was applied to IS incidence.…”

Serum n-6 polyunsaturated fatty acids and risk of atrial fibrillation: the Kuopio Ischaemic Heart Disease Risk Factor Study

“…In a multi-ethnic cohort of 6229 participants free of CVD (813 AF cases), plasma concentrations of n-6 PUFAs, particularly AA, were associated with lower risk of incident AF [ 9 ]. In a Mendelian randomization study among 588,190 individuals (65,446 AF cases), genetically-predicted higher plasma LA concentration, but not AA concentration, had a suggestive inverse association with the risk of AF [ 10 ]. This finding with LA is in contrast with the results of the Diet, Cancer and Health cohort study among 57,053 Danish individuals aged 50–65 years (2274 AF cases), where intakes of LA and AA were not associated with the risk of AF [ 11 ].…”

Using Genetic Variants to Evaluate the Causal Effect of Plasma Phospholipid Fatty Acids on Breast Cancer and Prostate Cancer: A Mendelian Randomization Study

“…Researchers have applied the MR approach to investigate the causal association between plasma phospholipid FAs and several diseases, including atrial fibrillation ( Yuan and Larsson, 2019 ), orthopedic diseases ( Yuan et al, 2020 ), cardiovascular diseases ( Yuan et al, 2019 ), and type 2 diabetes ( Yuan and Larsson, 2020 ). To our knowledge, we first used MR analysis to address this highly controversial issue, which avoids the reverse causality and confounders that result in bias in observational studies.…”