Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Creators: name: Shah, Sonia
name: Henry, Albert
name: Roselli, Carolina
name: Lin, Honghuang
name: Sveinbjörnsson, Garðar
name: Fatemifar, Ghazaleh
name: Hedman, Åsa K.
name: Wilk, Jemma B.
name: Morley, Michael P.
name: Chaffin, Mark D.
name: Helgadottir, Anna
name: Verweij, Niek
name: Dehghan, Abbas
name: Almgren, Peter
name: Andersson, Charlotte
name: Aragam, Krishna G.
name: Ärnlöv, Johan
name: Backman, Joshua D.
name: Biggs, Mary L.
name: Bloom, Heather L.
name: Brandimarto, Jeffrey
name: Brown, Michael R.
name: Buckbinder, Leonard
name: Carey, David J.
name: Chasman, Daniel I.
name: Chen, Xing
name: Chen, Xu
name: Chung, Jonathan
name: Chutkow, William
name: Cook, James P.
name: Delgado, Graciela E.
name: Denaxas, Spiros
name: Doney, Alexander S.
name: Dörr, Marcus
name: Dudley, Samuel C.
name: Dunn, Michael E.
name: Engström, Gunnar
name: Esko, Tõnu
name: Felix, Stephan B.
name: Finan, Chris
name: Ford, Ian
name: Ghanbari, Mohsen
name: Ghasemi, Sahar
name: Giedraitis, Vilmantas
name: Giulianini, Franco
name: Gottdiener, John S.
name: Gross, Stefan
name: Guðbjartsson, Daníel F.
name: Gutmann, Rebecca
name: Haggerty, Christopher M.
name: Van Der Harst, Pim
name: Hyde, Craig L.
name: Ingelsson, Erik
name: Jukema, J. Wouter
name: Kavousi, Maryam
name: Khaw, Kay-Tee
name: Kleber, Marcus E.
name: Køber, Lars
name: Koekemoer, Andrea
name: Langenberg, Claudia
name: Lind, Lars
name: Lindgren, Cecilia M.
name: London, Barry
name: Lotta, Luca A.
name: Lovering, Ruth C.
name: Luan, Jian’an
name: Magnusson, Patrik
name: Mahajan, Anubha
name: Margulies, Kenneth B.
name: März, Winfried
name: Melander, Olle
name: Mordi, Ify R.
name: Morgan, Thomas
name: Morris, Andrew D.
name: Morris, Andrew P.
name: Morrison, Alanna C.
name: Nagle, Michael W.
name: Nelson, Christopher P.
name: Niessner, Alexander
name: Niiranen, Teemu
name: O’Donoghue, Michelle L.
name: Owens, Anjali T.
name: Palmer, Colin N. A.
name: Parry, Helen M.
name: Perola, Markus
name: Portilla-Fernandez, Eliana
name: Psaty, Bruce M.
name: Rice, Kenneth M.
name: Ridker, Paul M.
name: Romaine, Simon P. R.
name: Rotter, Jerome I.
name: Salo, Perttu
name: Salomaa, Veikko
name: Van Setten, Jessica
name: Shalaby, Alaa A.
name: Smelser, Diane T.
name: Smith, Nicholas L.
name: Stender, Steen
name: Stott, David J.
name: Svensson, Per
name: Tammesoo, Mari-Liis
name: Taylor, Kent D.
name: Teder-Laving, Maris
name: Teumer, Alexander
name: Thorgeirsson, Guðmundur
name: Thorsteinsdottir, Unnur
name: Torp-Pedersen, Christian
name: Trompet, Stella
name: Tyl, Benoit
name: Uitterlinden, Andre G.
name: Veluchamy, Abirami
name: Völker, Uwe
name: Voors, Adriaan A.
name: Wang, Xiaosong
name: Wareham, Nicholas J.
name: Waterworth, Dawn
name: Weeke, Peter E.
name: Weiss, Raul
name: Wiggins, Kerri L.
name: Xing, Heming
name: Yerges-Armstrong, Laura M.
name: Yu, Bing
name: Zannad, Faiez
name: Zhao, Jing Hua
name: Hemingway, Harry
name: Samani, Nilesh J.
name: McMurray, John J. V.
name: Yang, Jian
name: Visscher, Peter M.
name: Newton-Cheh, Christopher
name: Malarstig, Anders
name: Holm, Hilma
name: Lubitz, Steven A.
name: Sattar, Naveed
name: Holmes, Michael V.
name: Cappola, Thomas P.
name: Asselbergs, Folkert W.
name: Hingorani, Aroon D.
name: Kuchenbaecker, Karoline
name: Ellinor, Patrick T.
name: Lang, Chim C.
name: Stefansson, Kari
name: Smith, J. Gustav
name: Vasan, Ramachandran S.
name: Swerdlow, Daniel I.
name: Lumbers, R. Thomas
name: Abecasis, Goncalo
name: Backman, Joshua
name: Bai, Xiaodong
name: Balasubramanian, Suganthi
name: Banerjee, Nilanjana
name: Baras, Aris
name: Barnard, Leland
name: Beechert, Christina
name: Blumenfeld, Andrew
name: Cantor, Michael
name: Chai, Yating
name: Coppola, Giovanni
name: Damask, Amy
name: Dewey, Frederick
name: Economides, Aris
name: Eom, Gisu
name: Forsythe, Caitlin
name: Fuller, Erin D.
name: Gu, Zhenhua
name: Gurski, Lauren
name: Guzzardo, Paloma M.
name: Habegger, Lukas
name: Hahn, Young
name: Hawes, Alicia
name: Van Hout, Cristopher
name: Jones, Marcus B.
name: Khalid, Shareef
name: Lattari, Michael
name: Li, Alexander
name: Lin, Nan
name: Liu, Daren
name: Lopez, Alexander
name: Manoochehri, Kia
name: Marchini, Jonathan
name: Marcketta, Anthony
name: Maxwell, Evan K.
name: McCarthy, Shane
name: Mitnaul, Lyndon J.
name: O’Dushlaine, Colm
name: Overton, John D.
name: Padilla, Maria Sotiropoulos
name: Paulding, Charles
name: Penn, John
name: Pradhan, Manasi
name: Reid, Jeffrey G.
name: Schleicher, Thomas D.
name: Schurmann, Claudia
name: Shuldiner, Alan
name: Staples, Jeffrey C.
name: Sun, Dylan
name: Toledo, Karina
name: Ulloa, Ricardo H.
name: Widom, Louis
name: Wolf, Sarah E.
name: Yadav, Ashish
name: Ye, Bin
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/631/208/205/2138
/631/443/592/2727
/692/699/75/230
/692/308/174
/45/43
article

description: Abstract: 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.