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Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.
Thursday,2025-04-10 11:07 America/Los_Angeles — ecterry
| Title | Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Henry, A, Mo, X, Finan, C, Chaffin, MD, Speed, D, Issa, H, Denaxas, S, Ware, JS, Zheng, SL, Mälarstig, A, Gratton, J, Bond, I, Roselli, C, Miller, D, Chopade, S, A Schmidt, F, Abner, E, Adams, L, Andersson, C, Aragam, KG, Arnlöv, J, Asselin, G, Raja, AAxelsson, Backman, JD, Bartz, TM, Biddinger, KJ, Biggs, ML, Bloom, HL, Boersma, E, Brandimarto, J, Brown, MR, Brunak, S, Bruun, MTopholm, Buckbinder, L, Bundgaard, H, Carey, DJ, Chasman, DI, Chen, X, Cook, JP, Czuba, T, de Denus, S, Dehghan, A, Delgado, GE, Doney, AS, Dörr, M, Dowsett, J, Dudley, SC, Engström, G, Erikstrup, C, Esko, T, Farber-Eger, EH, Felix, SB, Finer, S, Ford, I, Ghanbari, M, Ghasemi, S, Ghouse, J, Giedraitis, V, Giulianini, F, Gottdiener, JS, Gross, S, Guðbjartsson, DF, Gui, H, Gutmann, R, Hägg, S, Haggerty, CM, Hedman, ÅK, Helgadottir, A, Hemingway, H, Hillege, H, Hyde, CL, Jensen, BAagaard, J Jukema, W, Kardys, I, Karra, R, Kavousi, M, Kizer, JR, Kleber, ME, Køber, L, Koekemoer, A, Kuchenbaecker, K, Lai, Y-P, Lanfear, D, Langenberg, C, Lin, H, Lind, L, Lindgren, CM, Liu, PP, London, B, Lowery, BD, Luan, J'an, Lubitz, SA, Magnusson, P, Margulies, KB, Marston, NA, Martin, H, März, W, Melander, O, Mordi, IR, Morley, MP, Morris, AP, Morrison, AC, Morton, L, Nagle, MW, Nelson, CP, Niessner, A, Niiranen, T, Noordam, R, Nowak, C, O'Donoghue, ML, Ostrowski, SRye, Owens, AT, Palmer, CNA, Paré, G, Pedersen, OBirger, Perola, M, Pigeyre, M, Psaty, BM, Rice, KM, Ridker, PM, Romaine, SPR, Rotter, JI, Ruff, CT, Sabatine, MS, Sallah, N, Salomaa, V, Sattar, N, Shalaby, AA, Shekhar, A, Smelser, DT, Smith, NL, Sørensen, E, Srinivasan, S, Stefansson, K, Sveinbjörnsson, G, Svensson, P, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teumer, A, Thorgeirsson, G, Thorsteinsdottir, U, Torp-Pedersen, C, Tragante, V, Trompet, S, Uitterlinden, AG, Ullum, H, van der Harst, P, van Heel, D, van Setten, J, van Vugt, M, Veluchamy, A, Verschuuren, M, Verweij, N, Vissing, CRasmus, Völker, U, Voors, AA, Wallentin, L, Wang, Y, Weeke, PE, Wiggins, KL, L Williams, K, Yang, Y, Yu, B, Zannad, F, Zheng, C, Asselbergs, FW, Cappola, TP, Dubé, M-P, Dunn, ME, Lang, CC, Samani, NJ, Shah, S, Vasan, RS, J Smith, G, Holm, H, Shah, S, Ellinor, PT, Hingorani, AD, Wells, Q, R Lumbers, T |
| Corporate/Institutional Authors | Genes & Health Research Team, Estonian Biobank Research Team, DBDS Genomic Consortium, HERMES Consortium |
| Journal | Nat Genet |
| Date Published | 2025 Mar 04 |
| ISSN | 1546-1718 |
| Abstract | <p>Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.</p> |
| DOI | 10.1038/s41588-024-02064-3 |
| Alternate Journal | Nat Genet |
| PubMed ID | 40038546 |
| PubMed Central ID | 6952380 |
| Grant List | U01 AG068221 / AG / NIA NIH HHS / United States FS/18/65/34186 / / British Heart Foundation (BHF) / NIHR203328 / / DH | National Institute for Health Research (NIHR) / AA/18/6/34223 / / British Heart Foundation (BHF) / R21 HL175584 / HL / NHLBI NIH HHS / United States |
ePub date:
25/03