Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse

Cardiovasc Res. 2020 Jan 1;116(1):138-148. doi: 10.1093/cvr/cvz106.


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 = 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.

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 genome-wide association study to associate a locus with syncope and collapse.

Keywords: Genetic; Genome-wide association study; Syncope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cell Line
  • Chromosomes, Human, Pair 2*
  • Databases, Factual
  • Denmark / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Heredity
  • Humans
  • Incidence
  • Infant, Newborn
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Risk Assessment
  • Risk Factors
  • Syncope / diagnosis
  • Syncope / epidemiology
  • Syncope / genetics*
  • Syncope / physiopathology
  • United Kingdom / epidemiology
  • Young Adult


  • Kruppel-Like Transcription Factors
  • ZNF804A protein, human