Abstract
BackgroundThe causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF.MethodsSingle nucleotide polymorphisms (SNPs) related to smoking initiation (N = 374), age at initiation of regular smoking (N = 10), cigarettes per day (N = 55), and smoking cessation (N = 24) were derived from a genome-wide association studies (GWAS) of tobacco use (N = 1.2 million individuals). SNPs related to heavy alcohol use (N = 6) were derived from a GWAS of UK biobank (N = 125,249 individuals). The genetically matching instrumented variables were obtained from the GWAS of AF (N = 588,190 individuals). The estimates between tobacco and alcohol use and AF were combined by inverse-variance weighted (IVW), simple median, weighted median, MR-robust adjusted profile score method, MR-PRESSO, and multivariable MR.ResultsA total of 65,446 AF patients and 522,744 referents were included. In the IVW analysis, the odds ratio per one-unit increase of smoking initiation was 1.11 (95% CI, 1.06–1.16; P = 3.35 × 10−6) for AF. Genetically predicted age at initiation of regular smoking, cigarettes per day and smoking cessation were not associated with AF. The IVW estimate showed that heavy alcohol consumption increased AF risk (OR, 1.11; 95% CI, 1.04–1.18; P = 0.001). The results were consistent in complementary analyses and multivariable MR.ConclusionOur MR study indicated that regular smoking was associated with increased risk of AF, no matter the age at initiation of regular smoking, or the number of cigarettes smoked per day. Genetically predicted heavy alcohol consumption increased the risk of AF.
Highlights
The causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial
Tobacco use and AF Genetically predicted smoking initiation was associated with a higher risk of AF in the standard inverse-variance weighted (IVW) analysis, with an Odds ratio (OR) of 1.11
The association between genetically instrumented smoking initiation and AF was in line with complementary analyses using the multivariable Mendelian randomization (MR) adjusted for alcohol intake (OR, 1.10; 95% Confidence interval (CI), 1.02– 1.18), the simple median methods (OR, 1.11; 95% CI, 1.04–1.18), weighted median method (OR, 1.09; 95% CI, 1.01–1.17), and MR-robust adjusted profile scores (MR-RAPS) (OR, 1.13; 95% CI, 1.06–1.19) (Fig. 1)
Summary
The causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF. Cigarette smoking and alcohol intake are potential modifiable risk factors for atrial fibrillation (AF), which is the most common sustained arrhythmia and associated with an increased risk of stroke, heart failure and even death [1]. Several observational studies have suggested that smoking is associated with incident AF [2,3,4,5]. Mendelian randomization (MR) analysis is a method using instrumental variables associated with exposure to infer causality and interactions in observational studies Observational studies for causal inference were susceptible to confounding factors and reverse causal inference, which might result in an unreliable conclusion [12].
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