Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.
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Authors
Shah, SoniaHenry, Albert
Roselli, Carolina
Lin, Honghuang
Sveinbjörnsson, Garðar
Fatemifar, Ghazaleh
Hedman, Åsa K
Wilk, Jemma B
Morley, Michael P
Chaffin, Mark D
Helgadottir, Anna
Verweij, Niek
Dehghan, Abbas
Almgren, Peter
Andersson, Charlotte
Aragam, Krishna G
Ärnlöv, Johan
Backman, Joshua D
Biggs, Mary L
Bloom, Heather L
Brandimarto, Jeffrey
Brown, Michael R
Buckbinder, Leonard
Carey, David J
Chasman, Daniel I
Chen, Xing
Chen, Xu
Chung, Jonathan
Chutkow, William
Cook, James P
Delgado, Graciela E
Denaxas, Spiros
Doney, Alexander S
Dörr, Marcus
Dudley, Samuel C
Dunn, Michael E
Engström, Gunnar
Esko, Tõnu
Felix, Stephan B
Finan, Chris
Ford, Ian
Ghanbari, Mohsen
Ghasemi, Sahar
Giedraitis, Vilmantas
Giulianini, Franco
Gottdiener, John S
Gross, Stefan
Guðbjartsson, Daníel F
Gutmann, Rebecca
Haggerty, Christopher M
van der Harst, Pim
Hyde, Craig L
Ingelsson, Erik
Jukema, J Wouter
Kavousi, Maryam
Khaw, Kay-Tee
Kleber, Marcus E
Køber, Lars
Koekemoer, Andrea
Langenberg, Claudia
Lind, Lars
Lindgren, Cecilia M
London, Barry
Lotta, Luca A
Lovering, Ruth C
Luan, Jian'an
Magnusson, Patrik
Mahajan, Anubha
Margulies, Kenneth B
März, Winfried
Melander, Olle
Mordi, Ify R
Morgan, Thomas
Morris, Andrew D
Morris, Andrew P
Morrison, Alanna C
Nagle, Michael W
Nelson, Christopher P
Niessner, Alexander
Niiranen, Teemu
O'Donoghue, Michelle L
Owens, Anjali T
Palmer, Colin N A
Parry, Helen M
Perola, Markus
Portilla-Fernandez, Eliana
Psaty, Bruce M
Rice, Kenneth M
Ridker, Paul M
Romaine, Simon P R
Rotter, Jerome I
Salo, Perttu
Salomaa, Veikko
van Setten, Jessica
Shalaby, Alaa A
Smelser, Diane T
Smith, Nicholas L
Stender, Steen
Stott, David J
Svensson, Per
Tammesoo, Mari-Liis
Taylor, Kent D
Teder-Laving, Maris
Teumer, Alexander
Thorgeirsson, Guðmundur
Thorsteinsdottir, Unnur
Torp-Pedersen, Christian
Trompet, Stella
Tyl, Benoit
Uitterlinden, Andre G
Veluchamy, Abirami
Völker, Uwe
Voors, Adriaan A
Wang, Xiaosong
Wareham, Nicholas J
Waterworth, Dawn
Weeke, Peter E
Weiss, Raul
Wiggins, Kerri L
Xing, Heming
Yerges-Armstrong, Laura M
Yu, Bing
Zannad, Faiez
Zhao, Jing Hua
Hemingway, Harry
Samani, Nilesh J
McMurray, John J V
Yang, Jian
Visscher, Peter M
Newton-Cheh, Christopher
Malarstig, Anders
Holm, Hilma
Lubitz, Steven A
Sattar, Naveed
Holmes, Michael V
Cappola, Thomas P
Asselbergs, Folkert W
Hingorani, Aroon D
Kuchenbaecker, Karoline
Ellinor, Patrick T
Lang, Chim C
Stefansson, Kari
Smith, J Gustav
Vasan, Ramachandran S
Swerdlow, Daniel I
Lumbers, R Thomas
Issue Date
2020-01-09
Metadata
Show full item recordCitation
Shah S, Henry A, Roselli C, et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 2020;11(1):163. Published 2020 Jan 9. doi:10.1038/s41467-019-13690-5Abstract
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. 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 unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.Description
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAdditional Links
https://www.nature.com/articles/s41467-019-13690-5https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952380/
ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-13690-5
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