| Title | Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Roselli, C, Surakka, I, Olesen, MS, Sveinbjornsson, G, Marston, NA, Choi, SHoan, Holm, H, Chaffin, M, Gudbjartsson, D, Hill, MC, Aegisdottir, H, Albert, CM, Alonso, A, Anderson, CD, Arking, DE, Arnar, DO, Barnard, J, Benjamin, EJ, Braunwald, E, Brumpton, B, Campbell, A, Chami, N, Chasman, DI, Cho, K, Choi, E-K, Christophersen, IE, Chung, MK, Conen, D, Crijns, HJ, Cutler, MJ, Czuba, T, Damrauer, SM, Dichgans, M, Dörr, M, Dudink, E, Duong, TV, Erikstrup, C, Esko, T, Fatkin, D, Faul, JD, Ferreira, M, Freitag, DF, Ganesh, SK, J Gaziano, M, Geelhoed, B, Ghouse, J, Gieger, C, Giulianini, F, Graham, SE, Gudnason, V, Guo, X, Haggerty, C, Hayward, C, Heckbert, SR, Hveem, K, Ito, K, Johnson, R, J Jukema, W, Jurgens, SJ, Kääb, S, Kane, JP, Kany, S, Kardia, SLR, Kavousi, M, Khurshid, S, Kamanu, FK, Kirchhof, P, Kleber, ME, Knight, S, Komuro, I, Krieger, JE, Launer, LJ, Li, D, Lin, H, Lin, HJ, Loos, RJF, Lotta, L, Lubitz, SA, Lunetta, KL, Macfarlane, PW, Magnusson, PKE, Malik, R, Mantineo, H, Marcus, GM, März, W, McManus, DD, Melander, O, Melloni, GEM, Meyre, PB, Miyazawa, K, Mohanty, S, Monfort, LM, Müller-Nurasyid, M, Nafissi, NA, Natale, A, Nazarian, S, Ostrowski, SR, Pak, H-N, Pang, S, Pedersen, OB, Pedersen, NL, Pereira, AC, Pirruccello, JP, Preuss, M, Psaty, BM, Pullinger, CR, Rader, DJ, Rämö, JT, Ridker, PM, Rienstra, M, Risch, L, Roden, DM, Rotter, JI, Sabatine, MS, Schunkert, H, Shah, SH, Shim, J, M Shoemaker, B, Simonson, B, Sinner, MF, Smit, RAJ, Smith, JA, Smith, NL, J Smith, G, Soliman, EZ, Sørensen, E, Sotoodehnia, N, Strbian, D, Stricker, BH, Teder-Laving, M, Sun, YV, Thériault, S, Thorolfsdottir, RB, Thorsteinsdottir, U, Tveit, A, van der Harst, P, van Meurs, J, Wang, B, Weiss, S, Wells, QS, Weng, L-C, Wilson, PW, Xiao, L, Yang, P-S, Yao, J, Yoneda, ZT, Zeller, T, Zeng, L, Zhao, W, Zhou, X, Zöllner, S, Ruff, CT, Bundgaard, H, Willer, C, Stefansson, K, Ellinor, PT |
| Corporate/Institutional Authors | BioBank Japan Project, Regeneron Genetics Center, DBDS Genomic Consortium |
| Journal | Nat Genet |
| Volume | 57 |
| Issue | 3 |
| Pagination | 539-547 |
| Date Published | 2025 Mar |
| ISSN | 1546-1718 |
| Keywords | Atrial Fibrillation, Chromatin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Myocytes, Cardiac, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41588-024-02072-3 |
| Alternate Journal | Nat Genet |
| PubMed ID | 40050429 |
| PubMed Central ID | 2518320 |
| Grant List | R01 HL158071 / HL / NHLBI NIH HHS / United States |
