Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Sci Rep. 2021 Apr 19;11(1):8431. doi: 10.1038/s41598-021-87859-8.
Atrial fibrillation (AF) patients have enlarged left atria (LA), but prior studies suggested enlarged atria as both cause and consequence of AF. The aim of this study is to investigate the causal association between AF and LA size and function. In the UK Biobank, all individuals with contoured cardiovascular magnetic resonance data were selected. LA maximal volume (LA max), LA minimal volume (LA min), LA stroke volume and LA ejection fraction were measured and indexed to body surface area (BSA). Two-sample Mendelian randomization analyses were performed using 84 of the known genetic variants associated with AF to assess the association with all LA size and function in individuals without prevalent AF. A total of 4274 individuals (mean age 62.0 ± 7.5 years, 53.2% women) were included. Mendelian randomization analyses estimated a causal effect between genetically determined AF and BSA-indexed LA max, LA min, and LA ejection fraction, but not between AF and LA stroke volume. Leave-one-out analyses showed that the causal associations were attenuated after exclusion of rs67249485, located near PITX2 gene. Our results suggest that AF causally increases LA size and decreases LA ejection fraction. The AF risk allele of rs67249485, located near the PITX2 gene, contributes strongly to these associations.
心房颤动（AF）患者的左心房（LA）增大，但先前的研究表明，LA 增大既是 AF 的原因也是后果。本研究旨在探讨 AF 与 LA 大小和功能之间的因果关系。在英国生物库中，选择了所有具有轮廓心血管磁共振数据的个体。测量并将左心房最大容积（LA max）、左心房最小容积（LA min）、左心房每搏量和左心房射血分数与体表面积（BSA）进行指数化。使用与 AF 相关的 84 个已知遗传变异进行两样本孟德尔随机化分析，以评估在没有 AF 流行的个体中，所有 LA 大小和功能与 AF 的关联。共纳入 4274 名个体（平均年龄 62.0±7.5 岁，53.2%为女性）。孟德尔随机化分析估计了遗传决定的 AF 与 BSA 指数化的 LA max、LA min 和 LA 射血分数之间的因果关系，但与 LA 每搏量之间没有因果关系。逐一排除分析表明，在排除位于 PITX2 基因附近的 rs67249485 后，因果关系减弱。我们的结果表明，AF 可导致 LA 大小增加和 LA 射血分数降低。位于 PITX2 基因附近的 rs67249485 的 AF 风险等位基因强烈促成了这些关联。
