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.
Highlights
Atrial fibrillation (AF) is a prevalent chronic arrhythmia in adults [1] and a risk factor for ischemic stroke [2], heart failure [3], and death [4]
Linoleic acid; OA, oleic acid; PA, palmitic acid; POA, palmitoleic acid; SA, stearic acid; single-nucleotide polymorphisms (SNPs), singlenucleotide polymorphisms. This Mendelian randomization (MR) study is based on summary-level data from four large published genome-wide associations studies (GWASs) on plasma fatty acids [16,17,18] and AF [19]
AA indicates arachidonic acid; AF, atrial fibrillation; ALA, α-linolenic acid; Chr, chromosome; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EA, effect allele; EPA, eicosapentaenoic acid; Fatty acids (FAs), fatty acid; LA, linoleic acid; MUFA, monounsaturated fatty acid; NEA, none-effect allele; OA, oleic acid; PA, palmitic acid; POA, palmitoleic acid; polyunsaturated fatty acids (PUFAs), polyunsaturated fatty acid; SA, stearic acid; SE, standard error; SFA, saturated fatty acid; SNP, single–nucleotide polymorphisms. * The beta coefficients represent the change in percentage of total plasma fatty acid levels for each additional effect allele. † The beta coefficients represent the log odds ratio of atrial fibrillation for each additional effect allele
Summary
Atrial fibrillation (AF) is a prevalent chronic arrhythmia in adults [1] and a risk factor for ischemic stroke [2], heart failure [3], and death [4]. Most but not all observational studies observed null associations of dietary and circulating n-3 polyunsaturated fatty acid with the risk of AF [10,11,12,13]. 12 years, high n-3 polyunsaturated fatty acid intake was not associated with incident AF in men and women [10]. Observational studies are prone to residual confounding and reverse causality, which can bias the results in an unpredictable direction. Mendelian randomization (MR) is an epidemiological approach of diminishing misclassification of exposure, residual confounding, and reverse causality by utilizing genetic variants as instrumental. Reverse causality is eliminated as disease cannot modify genotype This method is based on instrumental variable analysis and can strengthen. Observational studies are prone to residual confounding and reverse causality, which can the inference on the causal nature of exposure-outcome associations.
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