| Title: |
Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases |
| Authors: |
Roselli,Carolina; Surakka,Ida; Olesen,Morten S; Sveinbjornsson,Gardar; Marston,Nicholas A; Choi,Seung Hoan; Holm,Hilma; Chaffin,Mark; Gudbjartsson,Daniel; Hill,Matthew C; Aegisdottir,Hildur; Albert,Christine M; Alonso,Alvaro; Anderson,Christopher D; Arking,Dan E; Arnar,David O; Barnard,John; Benjamin,Emelia J; Braunwald,Eugene; Brumpton,Ben; Campbell,Archie; Chami,Nathalie; Chasman,Daniel I; Cho,Kelly; Choi,Eue-Keun; Christophersen,Ingrid E; Chung,Mina K; Conen,David; Crijns,Harry J; Cutler,Michael J; Czuba,Tomasz; Damrauer,Scott M; Dichgans,Martin; Dörr,Marcus; Dudink,Elton; Duong,ThuyVy; Erikstrup,Christian; Esko,Tõnu; Fatkin,Diane; Faul,Jessica D; Ferreira,Manuel; Freitag,Daniel F; Ganesh,Santhi K; Gaziano,J Michael; Geelhoed,Bastiaan; Ghouse,Jonas; Gieger,Christian; Giulianini,Franco; Graham,Sarah E; van der Harst, Pim; BioBank Japan Project; DHL-Bedrijfsvoering; Circulatory Health; Gezonde Vaten |
| Publication Year: |
2025 |
| Subject Terms: |
Atrial Fibrillation/genetics; Chromatin/genetics; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Multifactorial Inheritance/genetics; Myocytes; Cardiac/metabolism; Polymorphism; Single Nucleotide; Risk Factors; Taverne; Journal Article; Meta-Analysis |
| Description: |
Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci. Furthermore, we assayed chromatin accessibility using assay for transposase-accessible chromatin with sequencing and histone H3 lysine 4 trimethylation in stem cell-derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility for our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known risk loci will facilitate a greater understanding of the pathways underlying AF. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
1061-4036 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/461036 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/461036 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CCFB0851 |
| Database: |
BASE |