BACKGROUND Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation. METHODS In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sample Mendelian randomization to consider the impact of birthweight on incident atrial fibrillation using summary data from the Early Growth Genetics Consortium GWAS of birthweight and a large biobank-based GWAS of atrial fibrillation. RESULTS Using the framework of 2-sample Mendelian randomization, we found that a 1-SD genetic elevation of birthweight was associated with increased risk of atrial fibrillation (odds ratio, 1.27 [95% CI, 1.14-1.41]; P=1×10-5) with sensitivity analyses demonstrating robustness of this result. CONCLUSIONS Our findings clarify the directionality of the relationship between birthweight and atrial fibrillation, supporting the growing body of evidence that intrauterine growth has a lifelong impact on cardiovascular health.

中文翻译：

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遗传决定的出生体重与心房颤动相关：一项孟德尔随机研究。

背景心房颤动是一种常见的心血管病症，其特征在于心脏上腔室中的不规则电活动。慢性心脏代谢危险因素和遗传学都已被证明有助于房颤的发展。出生体重也与心房颤动的风险有关。方法 在当前的研究中，我们利用遗传方法研究出生体重对心房颤动的影响。我们使用 2 样本孟德尔随机化来考虑出生体重对房颤事件的影响，使用来自早期生长遗传学联合会的出生体重 GWAS 和基于大型生物库的房颤 GWAS 的汇总数据。结果 使用 2 样本孟德尔随机化的框架，我们发现出生体重的 1-SD 遗传升高与心房颤动风险增加相关（优势比，1.27 [95% CI，1.14-1.41]；P=1×10-5），敏感性分析证明了这一结果的稳健性. 结论 我们的研究结果阐明了出生体重与心房颤动之间关系的方向性，支持越来越多的证据表明宫内生长对心血管健康具有终生影响。