Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah; Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah.
Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah; Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah.
JACC Clin Electrophysiol. 2019 Apr;5(4):493-500. doi: 10.1016/j.jacep.2019.01.002. Epub 2019 Feb 27.
The aim of this study was to define the population-based familial clustering of atrial fibrillation (AF) that is associated with fibrosis and describe evidence for a heritable predisposition.
Although a heritable contribution to AF is well-established and the association of fibrosis with AF is well-recognized, no studies have analyzed the genetic contribution to AF co-occurring with fibrosis.
AF patients with magnetic resonance imaging-confirmed fibrosis were identified in a population-based health sciences center database linked to a Utah genealogy. Familial clustering of AF/fibrosis was defined by analysis of pairwise case relatedness, estimation of relative risk of AF/fibrosis in relatives, and identification of high-risk AF/fibrosis pedigrees.
The 694 individuals identified with AF/fibrosis who had at least 3 generations of genealogy data were found to have significantly elevated pairwise relatedness (p < 0.001), even when first- and second-degree relationships were ignored (p < 0.001). Significantly elevated risks for AF/fibrosis among first- (relative risk [RR]: 4.65), second- (RR: 3.14), and third-degree (RR: 2.70) relatives of individuals with AF/fibrosis were observed. We identified 157 extended Utah pedigrees with a significant excess of AF/fibrosis among descendants.
There is a strong heritable contribution to predisposition to AF co-occurring with fibrosis. We suggest that this study provides a unique foundation for a search for predisposition genes, specifically for AF co-occurring with fibrosis.
本研究旨在定义与纤维化相关的房颤（AF）的基于人群的家族聚集，并描述遗传易感性的证据。
尽管 AF 具有遗传倾向已得到充分证实，并且纤维化与 AF 的相关性也得到广泛认可，但尚无研究分析与纤维化并存的 AF 的遗传贡献。
在一个与犹他州家谱相关联的基于人群的健康科学中心数据库中，确定了经磁共振成像证实存在纤维化的 AF 患者。通过分析成对病例的亲缘关系、估计亲属中 AF/纤维化的相对风险以及识别高风险 AF/纤维化家系来定义 AF/纤维化的家族聚集。
在 694 名具有 AF/纤维化且至少有 3 代家谱数据的个体中，发现存在显著升高的成对亲缘关系（p<0.001），即使忽略了一级和二级关系（p<0.001）。在 AF/纤维化个体的一级（相对风险 [RR]：4.65）、二级（RR：3.14）和三级（RR：2.70）亲属中，观察到 AF/纤维化的风险显著升高。我们确定了 157 个扩展的犹他州家系，其后代中 AF/纤维化的发生率明显过高。
存在与纤维化并存的 AF 易感性的强烈遗传贡献。我们建议，本研究为寻找易感性基因，特别是与纤维化并存的 AF 易感性基因，提供了独特的基础。
