ORCID: https://orcid.org/0000-0001-5267-6756; Surakka, Ida ORCID: https://orcid.org/0000-0002-6669-5541; Olesen, Morten S. ORCID: https://orcid.org/0000-0001-9477-5322; Sveinbjornsson, Gardar ORCID: https://orcid.org/0000-0003-2429-9468; Marston, Nicholas A. ORCID: https://orcid.org/0000-0001-6164-4617; Choi, Seung Hoan ORCID: https://orcid.org/0000-0002-2797-3190; Holm, Hilma ORCID: https://orcid.org/0000-0002-9517-6636; Chaffin, Mark ORCID: https://orcid.org/0000-0002-1234-5562; Gudbjartsson, Daniel F. ORCID: https://orcid.org/0000-0002-5222-9857; Hill, Matthew C.; Aegisdottir, Hildur; Albert, Christine M. ORCID: https://orcid.org/0000-0002-2081-1121; Alonso, Alvaro ORCID: https://orcid.org/0000-0002-2225-8323; Anderson, Christopher D. ORCID: https://orcid.org/0000-0002-0053-2002; Arking, Dan E. ORCID: https://orcid.org/0000-0001-8980-8695; Arnar, David O.; Barnard, John ORCID: https://orcid.org/0000-0003-2403-8268; Benjamin, Emelia J. ORCID: https://orcid.org/0000-0003-4076-2336; Braunwald, Eugene; Brumpton, Ben ORCID: https://orcid.org/0000-0002-3058-1059; Campbell, Archie ORCID: https://orcid.org/0000-0003-0198-5078; Chami, Nathalie ORCID: https://orcid.org/0000-0002-8547-6424; Chasman, Daniel I. ORCID: https://orcid.org/0000-0003-3357-0862; Cho, Kelly; Choi, Eue-Keun; Christophersen, Ingrid E.; Chung, Mina K.; Conen, David; Crijns, Harry J. ORCID: https://orcid.org/0000-0003-1073-5337; Cutler, Michael ORCID: https://orcid.org/0000-0001-9498-7472; Czuba, Tomasz ORCID: https://orcid.org/0009-0001-0232-0425; Damrauer, Scott M. ORCID: https://orcid.org/0000-0001-8009-1632; Dichgans, Martin ORCID: https://orcid.org/0000-0002-0654-387X; Dudink, Elton A. ORCID: https://orcid.org/0000-0003-4572-3969; Duong, ThuyVy ORCID: https://orcid.org/0000-0001-9733-440X; Erikstrup, Christian ORCID: https://orcid.org/0000-0001-6551-6647; Esko, Tõnu; Fatkin, Diane ORCID: https://orcid.org/0000-0002-9010-9856; Faul, Jessica D. ORCID: https://orcid.org/0000-0002-6969-6478; Ferreira, Manuel ORCID: https://orcid.org/0000-0001-9059-1825; Freitag, Daniel F.; Ganesh, Santhi K. ORCID: https://orcid.org/0000-0002-3663-5249; Gaziano, J. Michael; Geelhoed, Bastiaan; Ghouse, Jonas; Gieger, Christian ORCID: https://orcid.org/0000-0001-6986-9554; Giulianini, Franco; Graham, Sarah E. ORCID: https://orcid.org/0000-0003-1271-2489; Gudnason, Vilmundur ORCID: https://orcid.org/0000-0001-5696-0084; Guo, Xiuqing ORCID: https://orcid.org/0000-0002-5264-5068; Haggerty, Christopher; Hayward, Caroline ORCID: https://orcid.org/0000-0002-9405-9550; Heckbert, Susan R. ORCID: https://orcid.org/0000-0002-7100-512X; Hveem, Kristian; Ito, Kaoru ORCID: https://orcid.org/0000-0003-1843-773X; Johnson, Renee; Jukema, J. Wouter ORCID: https://orcid.org/0000-0002-3246-8359; Jurgens, Sean J. ORCID: https://orcid.org/0000-0002-1605-9782; Kääb, Stefan ORCID: https://orcid.org/0000-0001-8824-3581; Kane, John P.; Kany, Shinwan; Kardia, Sharon L. R.; Kavousi, Maryam ORCID: https://orcid.org/0000-0001-5976-6519; Khurshid, Shaan; Kamanu, Frederick K. ORCID: https://orcid.org/0000-0001-7208-1047; Kirchhof, Paulus ORCID: https://orcid.org/0000-0002-1881-0197; Kleber, Marcus E. ORCID: https://orcid.org/0000-0003-0663-7275; Knight, Stacey; Komuro, Issei; Krieger, Jose E.; Launer, Lenore J. ORCID: https://orcid.org/0000-0002-3238-7612; Li, Dadong; Lin, Honghuang ORCID: https://orcid.org/0000-0003-3043-3942; Lin, Henry J. ORCID: https://orcid.org/0000-0001-6771-0486; Loos, Ruth J. F. ORCID: https://orcid.org/0000-0002-8532-5087; Lotta, Luca A. ORCID: https://orcid.org/0000-0002-2619-5956; Lubitz, Steven A. ORCID: https://orcid.org/0000-0002-9599-4866; Lunetta, Kathryn L. ORCID: https://orcid.org/0000-0002-9268-810X; Macfarlane, Peter W. ORCID: https://orcid.org/0000-0002-5390-1596; Magnusson, Patrik K. E. ORCID: https://orcid.org/0000-0002-7315-7899; Malik, Rainer ORCID: https://orcid.org/0000-0001-9212-2520; Mantineo, Helene; Marcus, Gregory M. ORCID: https://orcid.org/0000-0001-5197-7696; März, Winfried ORCID: https://orcid.org/0000-0001-6083-8946; McManus, David D.; Melander, Olle; Melloni, Giorgio E. M. ORCID: https://orcid.org/0000-0001-6371-1334; Meyre, Pascal B. ORCID: https://orcid.org/0000-0002-1236-1386; Miyazawa, Kazuo; Mohanty, Sanghamitra; Monfort, Laia M.; Müller-Nurasyid, Martina ORCID: https://orcid.org/0000-0003-3793-5910; Nafissi, Navid A. ORCID: https://orcid.org/0000-0003-0706-9548; Natale, Andrea; Nazarian, Saman; Ostrowski, Sisse R. ORCID: https://orcid.org/0000-0001-5288-3851; Pak, Hui-Nam ORCID: https://orcid.org/0000-0002-3256-3620; Pang, Shichao; Pedersen, Ole B. ORCID: https://orcid.org/0000-0003-2312-5976; Pedersen, Nancy L. ORCID: https://orcid.org/0000-0001-8057-3543; Pereira, Alexandre C. ORCID: https://orcid.org/0000-0002-7782-5540; Pirruccello, James P. ORCID: https://orcid.org/0000-0001-6088-4037; Preuss, Michael H. ORCID: https://orcid.org/0000-0001-5266-8465; Psaty, Bruce M. ORCID: https://orcid.org/0000-0002-7278-2190; Pullinger, Clive R.; Rader, Daniel J. ORCID: https://orcid.org/0000-0002-9245-9876; Rämö, Joel T. ORCID: https://orcid.org/0000-0002-6429-5149; Ridker, Paul M.; Rienstra, Michiel ORCID: https://orcid.org/0000-0002-2581-070X; Risch, Lorenz ORCID: https://orcid.org/0000-0003-2692-6699; Roden, Dan M. ORCID: https://orcid.org/0000-0002-6302-0389; Rotter, Jerome I. ORCID: https://orcid.org/0000-0001-7191-1723; Sabatine, Marc S.; Schunkert, Heribert ORCID: https://orcid.org/0000-0001-6428-3001; Shah, Svati H.; Shim, Jaemin; Shoemaker, M. Benjamin; Simonson, Bridget; Sinner, Moritz F. ORCID: https://orcid.org/0000-0002-6660-796X; Smit, Roelof A. J. ORCID: https://orcid.org/0000-0001-9822-6726; Smith, Jennifer A. ORCID: https://orcid.org/0000-0002-3575-5468; Smith, Nicholas L. ORCID: https://orcid.org/0000-0003-3483-353X; Smith, J. Gustav; Soliman, Elsayed Z. ORCID: https://orcid.org/0000-0001-5632-8150; Sørensen, Erik ORCID: https://orcid.org/0000-0002-5002-9077; Sotoodehnia, Nona ORCID: https://orcid.org/0000-0002-2705-6237; Strbian, Daniel ORCID: https://orcid.org/0000-0001-9095-2344; Stricker, Bruno H.; Teder-Laving, Maris ORCID: https://orcid.org/0000-0002-5872-1850; Sun, Yan V. ORCID: https://orcid.org/0000-0002-2838-1824; Thériault, Sébastien ORCID: https://orcid.org/0000-0003-1893-8307; Thorolfsdottir, Rosa B. ORCID: https://orcid.org/0000-0001-7475-0398; Thorsteinsdottir, Unnur; Tveit, Arnljot; Harst, Pim van der ORCID: https://orcid.org/0000-0002-2713-686X; Meurs, Joyce van; Wang, Biqi; Weiss, Stefan ORCID: https://orcid.org/0000-0002-3553-4315; Wells, Quinn S.; Weng, Lu-Chen ORCID: https://orcid.org/0000-0003-1475-4930; Wilson, Peter W. F. 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(2025):
Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.
In: Nature Genetics, Bd. 57: S. 539-547
Abstract
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.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
Medizin > Munich Cluster for Systems Neurology (SyNergy) Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik I (Kardiologie) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 1061-4036 |
| Sprache: | Englisch |
| Dokumenten ID: | 124905 |
| Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2025 14:29 |
| Letzte Änderungen: | 02. Apr. 2025 14:29 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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