Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Mar 21;44(12):1070-1080.
doi: 10.1093/eurheartj/ehad016.

Genetic variants associated with syncope implicate neural and autonomic processes

Hildur M Aegisdottir  1   2 , Rosa B Thorolfsdottir  1 , Gardar Sveinbjornsson  1 , Olafur A Stefansson  1 , Bjarni Gunnarsson  1 , Vinicius Tragante  1 , Gudmar Thorleifsson  1 , Lilja Stefansdottir  1 , Thorgeir E Thorgeirsson  1 , Egil Ferkingstad  1 , Patrick Sulem  1 , Gudmundur Norddahl  1 , Gudrun Rutsdottir  1 , Karina Banasik  3 , Alex Hoerby Christensen  4   5   6 , Christina Mikkelsen  7   8 , Ole Birger Pedersen  6   9 , Søren Brunak  3 , Mie Topholm Bruun  10 , Christian Erikstrup  11   12 , Rikke Louise Jacobsen  7 , Kaspar Rene Nielsen  13 , Erik Sørensen  7 , Michael L Frigge  1 , Kristjan E Hjorleifsson  1 , Erna V Ivarsdottir  1 , Anna Helgadottir  1 , Solveig Gretarsdottir  1 , Valgerdur Steinthorsdottir  1 , Asmundur Oddsson  1 , Hannes P Eggertsson  1 , Gisli H Halldorsson  1 , David A Jones  14 , Jeffrey L Anderson  15   16 , Kirk U Knowlton  15   17 , Lincoln D Nadauld  14   18 ; DBDS Genomic Consortium; Magnus Haraldsson  2   19 , Gudmundur Thorgeirsson  1   2   20 , Henning Bundgaard  6   21 , David O Arnar  1   2   20 , Unnur Thorsteinsdottir  1   2 , Daniel F Gudbjartsson  1   22 , Sisse R Ostrowski  6   7 , Hilma Holm  1 , Kari Stefansson  1   2
Collaborators, Affiliations
Meta-Analysis

Genetic variants associated with syncope implicate neural and autonomic processes

Hildur M Aegisdottir et al. Eur Heart J. .

Erratum in

Abstract

Aims: Syncope is a common and clinically challenging condition. In this study, the genetics of syncope were investigated to seek knowledge about its pathophysiology and prognostic implications.

Methods and results: This genome-wide association meta-analysis included 56 071 syncope cases and 890 790 controls from deCODE genetics (Iceland), UK Biobank (United Kingdom), and Copenhagen Hospital Biobank Cardiovascular Study/Danish Blood Donor Study (Denmark), with a follow-up assessment of variants in 22 412 cases and 286 003 controls from Intermountain (Utah, USA) and FinnGen (Finland). The study yielded 18 independent syncope variants, 17 of which were novel. One of the variants, p.Ser140Thr in PTPRN2, affected syncope only when maternally inherited. Another variant associated with a vasovagal reaction during blood donation and five others with heart rate and/or blood pressure regulation, with variable directions of effects. None of the 18 associations could be attributed to cardiovascular or other disorders. Annotation with regard to regulatory elements indicated that the syncope variants were preferentially located in neural-specific regulatory regions. Mendelian randomization analysis supported a causal effect of coronary artery disease on syncope. A polygenic score (PGS) for syncope captured genetic correlation with cardiovascular disorders, diabetes, depression, and shortened lifespan. However, a score based solely on the 18 syncope variants performed similarly to the PGS in detecting syncope risk but did not associate with other disorders.

Conclusion: The results demonstrate that syncope has a distinct genetic architecture that implicates neural regulatory processes and a complex relationship with heart rate and blood pressure regulation. A shared genetic background with poor cardiovascular health was observed, supporting the importance of a thorough assessment of individuals presenting with syncope.

Keywords: PTPRN2; GWAS; Imprinting; Meta-analysis; Syncope; Vasovagal reaction.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: The following authors are employees of deCODE genetics/Amgen, Inc.: Hildur M Aegisdottir, Rosa B Thorolfsdottir, Gardar Sveinbjornsson, Olafur A Stefansson, Bjarni Gunnarsson, Vinicius Tragante, Lilja Stefansdottir, Thorgeir E Thorgeirsson, Egil Ferkingstad, Gudmar Thorleifsson, Michael L Frigge, Kristjan E Hjorleifsson, Erna V Ivarsdottir, Anna Helgadottir, Solveig Gretarsdottir, Valgerdur Steinthorsdottir, Asmundur Oddsson, Hannes P Eggertsson, Gisli H Halldorsson, Patrick Sulem, Gudmundur Norddahl, Gudrun Rutsdottir, Gudmundur Thorgeirsson, David O Arnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, and Kari Stefansson. Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001).

Comment in

Publication types