AIMS: 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.

METHODS AND RESULTS: 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 [OR]= 1.13, 95% confidence interval [CI] 1.10-1.17, P = 5.8x10-15), with lead single nucleotide polymorphism (SNP) rs12465214 in proximity to the gene ZNF804A. This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (HR = 1.30, 95% CI 1.15-1.46, P = 1.68x10-5) of incident syncope. qPCR analysis showed ZNF804A to be expressed most abundantly in brain tissue.

CONCLUSION: 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 GWAS to associate a locus with syncope and collapse.