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

被引：17

作者：

Hadji-Turdeghal, Katra ^{[1
,2
,3
]}

Andreasen, Laura ^{[1
,2
,3
]}

Hagen, Christian M. ^{[4
,5
]}

Ahlberg, Gustav ^{[1
,2
,3
]}

Ghouse, Jonas ^{[1
,2
,3
]}

Baekvad-Hansen, Marie ^{[4
,5
]}

Bybjerg-Grauholm, Jonas ^{[4
,5
]}

Hougaard, David M. ^{[4
,5
]}

Hedley, Paula ^{[4
,5
]}

Haunso, Stig ^{[1
,2
,6
]}

Svendsen, Jesper H. ^{[1
,2
,6
]}

Kanters, Jorgen K. ^{[7
]}

Jepps, Thomas A. ^{[3
]}

Skov, Morten W. ^{[1
,2
,3
]}

Christiansen, Michael ^{[4
,5
,7
]}

Olesen, Morten S. ^{[1
,2
,3
]}

机构：

[1] Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Lab Mol Cardiol,Heart Ctr, Copenhagen, Denmark

[2] Danish Natl Res Fdn Ctr Cardiac Arrhythmia, Copenhagen, Denmark

[3] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark

[4] Statens Serum Inst, Dept Congenital Disorders, Copenhagen, Denmark

[5] Lundbeck Fdn Initiat Integrat Psychiat Res, IPSYCH, Copenhagen, Denmark

[6] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark

[7] Univ Copenhagen, Dept Biomed Sci, Lab Expt Cardiol, Copenhagen, Denmark

来源：

CARDIOVASCULAR RESEARCH | 2020年 / 116卷 / 01期

关键词：

Syncope; Genetic; Genome-wide association study; GENE; SCHIZOPHRENIA; RECEPTOR; POLYMORPHISM; DIAGNOSIS; PROTEIN; COHORT;

D O I：

10.1093/cvr/cvz106

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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 x 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.

引用

页码：138 / 148

页数：11

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