Genetically determined tobacco and alcohol use and risk of atrial fibrillation

Abstract

Background 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. Methods Single 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. Results A 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. Conclusion Our 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.

Causal Association Between Alcohol Consumption and Atrial Fibrillation: A Mendelian Randomization Study

“…In the two-sample MR study performed by Jiang et al, 16) genetically predicted alcohol consumption was not associated with AF. However, in the study by Larsson et al, 17) genetically predicted alcohol consumption was positively associated with AF, and in the study by Lu et al, 18) a positive relationship was found between genetically predicted heavy drinking (>35 units/week in women and >50 units/week in men) and AF.…”

“…As all studies did not use the ALDH2 gene as an IV, their results may not be applicable for the East Asian population. 16) 17) 18) In the present study, we performed the MR analysis using ALDH2 rs671 to examine the causal association between alcohol and AF in Korea.…”

Appraising the causal role of smoking in multiple diseases: A systematic review and meta-analysis of Mendelian randomization studies

“…During the last few years, the potential causal association between smoking and risk of different diseases has been investigated using the Mendelian randomization (MR) approach. 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 MR is a method that utilizes genetic variants associated with a difference in the exposure (e.g., smoking liability) as instrumental variable for the exposure to determine the causal role of the exposure in the development of disease. 33 The MR design mitigates confounding because genetic alleles are randomly allocated when passed from parents to offspring and therefore usually not related to other risk factors.…”

Assessment of the Causal Effects of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study

“…Moreover, despite epidemiological studies demonstrating the potential associations between OSA and AF, this evidence might be subject to residual confounding factors, as both OSA and AF shared several risk factors: at least 70% of OSA patients are obese (32), even MR analysis assessing the causality between genetic predicted BMI and OSA confirmed their strong genetic correlations (14), and a causal relationship was also identified between genetically predicted obesity and risk of AF (33,34); so that obesity was an extremely important common factor as it was predisposed to result in the co-phenomenon of OSA and AF even in longitudinal studies. Apart from obesity, the habits of smoking (35,36) and alcohol intake (37,38) also tended to act as common risks of OSA and AF. With an instrumental variable analysis and a huge sample size, the MR approach can be used to study a cause-and-effect relationship without interferences of bias and confounding that are hard to circumvent in observational design, thus it is more appropriate for our exposure and outcome set.…”