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

Katra Hadji-Turdeghal, Laura Andreasen, Christian M Hagen, Gustav Ahlberg, Jonas Ghouse, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, David M Hougaard, Paula Hedley, Stig Haunsø, Jesper H Svendsen, Jørgen K Kanters, Thomas A Jepps, Morten W Skov, Michael Christiansen, Morten S Olesen

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Abstract

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.

Original languageEnglish
JournalCardiovascular Research
Volume116
Issue number1
Pages (from-to)138-148
ISSN0008-6363
DOIs
Publication statusPublished - 2020

Bibliographical note

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

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