INTRODUCTION The relationship between smoking and heart disease has been frequently reported. Therefore, we aimed to explore the association between smoking initiation and atrial fibrillation. METHODS Genetic association data pertaining to smoking initiation and atrial fibrillation were obtained from genome-wide association studies (GWAS). Phenotypically related single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Inverse-variance weighted (IVW), weighted median, Mendelian randomization (MR), Egger regression, simple mode, and weighted mode methods were employed to perform the MR study. The association between smoking initiation and atrial fibrillation was evaluated using odds ratios (OR) and 95% confidence intervals (CI). Cochran's Q test was employed to assess heterogeneity among instrumental variables, utilizing the IVW and MR-Egger methods. The Egger-intercept method was employed to test for horizontal pleiotropy, and the 'leave-one-out' method was utilized for sensitivity analysis. RESULTS The MR results for the effect of smoking initiation on atrial fibrillation (IVW, OR=1.11; 95% CI: 1.02-1.20, p=0.013) supported an association between smoking initiation and an increased likelihood of atrial fibrillation. In total, 85 SNPs were extracted from the GWAS pooled data as instrumental variables. The MR-Egger method indicated an intercept close to 0 (Egger intercept= -0.005, p=0.371), suggesting no horizontal pleiotropy in the selected instrumental variables. The 'leave-one-out' sensitivity analysis demonstrated that the results were robust and that no instrumental variables significantly influenced the results. Reverse MR analysis indicated no effect of atrial fibrillation on smoking initiation (IVW, OR=1.00; 95% CI: 0.99-1.02, p=0.684). CONCLUSIONS Smoking initiation has a significant impact on atrial fibrillation. However, atrial fibrillation did not influence smoking initiation. This study provides novel insights into the genetic relationships between smoking initiation and atrial fibrillation.

中文翻译：

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吸烟与心房颤动之间关联的双向双样本孟德尔随机化研究。


引言 吸烟与心脏病之间的关系已被频繁报道。因此，我们旨在探讨吸烟与心房颤动之间的关联。方法 从全基因组关联研究 (GWAS) 中获得与吸烟和心房颤动有关的遗传关联数据。选择表型相关的单核苷酸多态性（SNP）作为工具变量。采用逆方差加权（IVW）、加权中位数、孟德尔随机化（MR）、艾格回归、简单模式和加权模式方法进行MR研究。使用比值比 (OR) 和 95% 置信区间 (CI) 评估开始吸烟与心房颤动之间的关联。 Cochran 的 Q 检验利用 IVW 和 MR-Egger 方法来评估工具变量之间的异质性。采用 Egger 截距法检验水平多效性，并采用“留一法”进行敏感性分析。结果 开始吸烟对心房颤动影响的 MR 结果（IVW，OR=1.11；95% CI：1.02-1.20，p=0.013）支持开始吸烟与心房颤动可能性增加之间的关联。从 GWAS 汇总数据中总共提取了 85 个 SNP 作为工具变量。 MR-Egger 方法表明截距接近 0（Egger 截距= -0.005，p=0.371），表明所选工具变量不存在水平多效性。 “留一法”敏感性分析表明结果是稳健的，并且没有工具变量对结果产生显着影响。反向 MR 分析表明心房颤动对开始吸烟没有影响（IVW，OR=1.00；95% CI：0.99-1.02，p=0.684）。 结论 开始吸烟对心房颤动有显着影响。然而，心房颤动并不影响吸烟的开始。这项研究为吸烟与心房颤动之间的遗传关系提供了新的见解。