| Autor: |
Stefan Gross, Honghuang Lin, Diane T. Smelser, März W, Niek Verweij, Alexander Niessner, Peter M. Visscher, Ruth C. Lovering, Erik Ingelsson, Nicholas L. Smith, Lars Lind, Jerome I. Rotter, Anna Helgadottir, David J. Stott, Michelle L. O'Donoghue, Daniel I. Chasman, Karoline Kuchenbaecker, Morris Ad, Michael W. Nagle, Morris Ap, Steven A. Lubitz, Giedraitis, Abirami Veluchamy, Paul M. Ridker, David J. Carey, Benoit Tyl, Carolina Roselli, Laura M. Yerges-Armstrong, Michael R. Brown, Faiez Zannad, Aroon D. Hingorani, Åsa K. Hedman, Nilesh J. Samani, Daníel F. Guðbjartsson, Maris Teder-Laving, Stephan B. Felix, Christopher Newton-Cheh, Marcus Dörr, Thomas P. Cappola, Daniel I. Swerdlow, Leonard Buckbinder, Xiaosong Wang, Alex S. F. Doney, C. Andersson, Jonathan H. Chung, Joshua D. Backman, Tõnu Esko, Mohsen Ghanbari, Joop Jukema, Ian Ford, Gunnar Engström, Kent D. Taylor, Johan Ärnlöv, P.E Weeke, Kenneth B. Margulies, Peter Svensson, Folkert W. Asselbergs, Lars Køber, Michael V. Holmes, Anders Mälarstig, Chim C. Lang, Krishna G. Aragam, Samuel C. Dudley, Christian Torp-Pedersen, Bruce M. Psaty, Alexander Teumer, John J.V. McMurray, Raul Weiss, Smith Jg, Patrick T. Ellinor, Anjali T. Owens, Ify R. Mordi, G Sveinbjörnsson, Luca A. Lotta, John S. Gottdiener, Christopher M. Haggerty, Christopher P. Nelson, C M Lindgren, Hilma Holm, Michael E. Dunn, Albert Henry, Helen M. Parry, Salomaa, Huilin Xing, Kenneth Rice, Marcus E. Kleber, Spiros Denaxas, Chris Finan, Xu Chen, Unnur Thorsteinsdottir, Naveed Sattar, Bing Yu, Kerri L. Wiggins, Alaa Shalaby, Romaine Spr., Patrik K. E. Magnusson, Adriaan A. Voors, Lumbers Rt, Stella Trompet, Maryam Kavousi, Kari Stefansson, Jian'an Luan, Harry Hemingway, van Setten J, Anubha Mahajan, Olle Melander, Uwe Völker, Peter Almgren, Chaffin, Palmer Cna., Eliana Portilla-Fernandez, Stefan Stender, Markus Perola, Guðmundur Thorgeirsson, Ghazaleh Fatemifar, Teemu J. Niiranen, Nicholas J. Wareham, Andrea Koekemoer, James P. Cook, Jeff Brandimarto, Jian Yang, Mary L. Biggs, Claudia Langenberg, Perttu Salo, Sonia Shah, A.G. Uitterlinden, Mari-Liis Tammesoo, Jemma B. Wilk, Craig L. Hyde, Graciela E. Delgado, van der Harst P, Alanna C. Morrison, Kay-Tee Khaw, Barry London, Rebecca Gutmann, Thomas M. Morgan, Franco Giulianini, Abbas Dehghan, Heather L. Bloom, William A. Chutkow, Dawn M. Waterworth, Ramachandran S. Vasan, Jing Hua Zhao, Morley Mp, Sahar Ghasemi |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/682013 |
| Popis: |
Heart failure (HF) is a leading cause of morbidity and mortality worldwide1. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained2–4. We report the largest GWAS meta-analysis of HF to-date, comprising 47,309 cases and 930,014 controls. We identify 12 independent variant associations with HF at 11 genomic loci, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function suggesting shared genetic aetiology. Expression quantitative trait analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent effects for atrial fibrillation, body mass index, hypertension and triglycerides. These findings extend our knowledge of the genes and pathways underlying HF and may inform the development of new therapeutic approaches. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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