TY - JOUR
T1 - Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse
AU - Hadji-Turdeghal, Katra
AU - Andreasen, Laura
AU - Hagen, Christian M
AU - Ahlberg, Gustav
AU - Ghouse, Jonas
AU - Bækvad-Hansen, Marie
AU - Bybjerg-Grauholm, Jonas
AU - Hougaard, David M
AU - Hedley, Paula
AU - Haunsø, Stig
AU - Svendsen, Jesper H
AU - Kanters, Jørgen K
AU - Jepps, Thomas A
AU - Skov, Morten W
AU - Christiansen, Michael
AU - Olesen, Morten S
N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
U2 - 10.1093/cvr/cvz106
DO - 10.1093/cvr/cvz106
M3 - Journal article
C2 - 31049583
SN - 0008-6363
JO - Cardiovascular Research
JF - Cardiovascular Research
ER -