[1] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [4] These authors contributed equally to this work.
Nat Genet. 2010 Mar;42(3):240-4. doi: 10.1038/ng.537. Epub 2010 Feb 21.
Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
心房颤动（AF）是最常见的持续性心律失常。先前的研究已经确定了几个与典型 AF 相关的遗传位点。我们试图确定孤独性 AF 的常见遗传变异。这种情况影响了一部分没有明显心脏病且 AF 遗传率增加的个体。我们报告了一项使用 1335 例孤独性 AF（病例）和 12844 例无影响个体（参照）进行的全基因组关联研究的荟萃分析。病例来自德国 AF 网络、心脏和血管健康研究、社区动脉粥样硬化风险研究、克利夫兰诊所和马萨诸塞州总医院。我们在 1q21 染色体上发现了与孤独性 AF 的关联（rs13376333，调整后的优势比=1.56；P=6.3×10(-12)），并在两个具有孤独性 AF 的独立队列中复制了这一关联（总体合并优势比=1.52，95%置信区间 1.40-1.64；P=1.83×10(-21)）。rs13376333 位于 KCNN3 的内含子中，该基因编码一种参与心房复极的钾通道蛋白。
