UNASSIGNED: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies.
UNASSIGNED: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A, SCN10A, and TTN/CCDC141. Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals.
UNASSIGNED: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.
■我们进行了全基因组关联研究的多血统荟萃分析,以确定AVNRT(4项研究)和AVAP/AVRT(7项研究)的遗传基因座。我们通过分析相关变异与心脏基因表达之间的关系,评估了支持候选基因潜在因果效应的证据。进行全转录组分析,并检查先前的全基因组关联研究。
■分析包括2384例AVNRT病例和106489例参考,和2811个AVAP/AVRT案例和1,483093个参考。我们确定了2个明显的AVNRT位点,这表明NKX2-5和TTN是疾病易感基因。全转录组关联分析支持预测的NKX2-5心脏表达降低与AVNRT之间的关联。我们确定了AVAP/AVRT的3个重要基因座,这牵涉到SCN5A,SCN10A,和TTN/CCDC141。先前已经报道了心脏表型的几个基因座的变异关联,包括心房颤动,中风,Brugada综合征,和心电图间隔。
■我们的发现突出了与离子通道功能(AVAP/AVRT)相关的基因区域,以及心脏发育和肌节(AVAP/AVRT和AVNRT)是室上性心动过速易感性的重要潜在效应因子。