Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark.
Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark.
Cardiovasc Res. 2020 Jan 1;116(1):138-148. doi: 10.1093/cvr/cvz106.
Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse.
We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10-1.17, P = 5.8 × 10-15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15-1.46, P = 1.68 × 10-5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue.
We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.
晕厥是一种常见病症，常导致住院或频繁就诊于急诊。家族聚集性和双胞胎研究表明，晕厥具有遗传成分。我们研究了常见的遗传变异是否易导致晕厥和晕厥发作。
我们使用英国生物库研究中 408961 名具有欧洲血统的个体的晕厥全基因组关联数据。在一项复制研究中，我们使用综合精神病学研究联盟（iPSYCH）队列（n=86189），根据基因型携带者状态分层，研究晕厥发作的风险。我们报告了一个位于染色体 2q32.1 上的全基因组显著位置[比值比=1.13，95%置信区间（CI）1.10-1.17，P=5.8×10-15]，与基因锌指蛋白 804a（ZNF804A）附近的 SNP rs12465214相关。该关联在 iPSYCH 队列中也得到了证实，C 等位基因纯合携带者发生晕厥的风险比（1.30，95%CI 1.15-1.46，P=1.68×10-5）增加。定量聚合酶链反应分析显示，ZNF804A 在脑组织中表达最丰富。
我们确定了与晕厥和晕厥发作相关的全基因组显著位置（rs12465214）。该关联在独立队列中得到了复制。这是首次全基因组关联研究将一个基因座与晕厥和晕厥发作相关联。
