Skip to Main content Skip to Navigation
Journal articles

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Sonia Shah 1, 2 Albert Henry 2 Carolina Roselli 3, 4 Honghuang Lin 5, 6 Garðar Sveinbjörnsson 7 Ghazaleh Fatemifar 2 Åsa Hedman 8 Jemma Wilk 9 Michael Morley 10 Mark Chaffin 3 Anna Helgadottir 7 Niek Verweij 3, 11 Abbas Dehghan 12 Peter Almgren 13 Charlotte Andersson 3, 14 Krishna Aragam 3, 15 Johan Ärnlöv 16, 17 Joshua Backman 18 Mary Biggs 19, 20 Heather Bloom 21 Jeffrey Brandimarto 10 Michael Brown 22 Leonard Buckbinder 9 David Carey 23 Daniel Chasman 24, 25 Xing Chen 9 Xu Chen 8 Jonathan Chung 26 William Chutkow 27 James Cook 28 Graciela Delgado 29, 30 Spiros Denaxas 2, 31 Alexander Doney 32 Marcus Dörr 33, 34 Samuel Dudley 35 Michael Dunn 36 Gunnar Engström 37 Tonu Esko 38, 3 Stephan Felix 33, 34 Chris Finan 2 Ian Ford 39 Mohsen Ghanbari 40, 41 Sahar Ghasemi 33, 34 Vilmantas Giedraitis 42 Franco Giulianini 43 John Gottdiener 44 Stefan Gross 33, 34 Daníel Guðbjartsson 7, 45 Rebecca Gutmann 46 Christopher Haggerty 47 Pim van der Harst 48, 4 Craig Hyde 9 Erik Ingelsson 49, 50, 51 J. Wouter Jukema 52, 53 Maryam Kavousi 41 Kay-Tee Khaw 54 Marcus Kleber 29 Lars Køber 55, 56 Andrea Koekemoer 57, 58 Claudia Langenberg 59 Lars Lind 51 Cecilia Lindgren 3, 60 Barry London 61 Luca Lotta 62 Ruth Lovering 2 Jian’an Luan 62 Patrik Magnusson 62 Anubha Mahajan 63 Kenneth Margulies 10 Winfried März 64, 28, 65 Olle Melander 13, 66 Ify Mordi 32 Thomas Morgan 67, 27 Andrew D. Morris 68 Andrew P. Morris 63, 28 Alanna C. Morrison 22 Michael Nagle 9 Christopher Nelson 69 Alexander Niessner 70 Teemu Niiranen 71, 72 Michelle O’donoghue 73 Anjali Owens 10 Colin Palmer 32 Helen Parry 32 Markus Perola 71 Eliana Portilla-Fernandez 41 Bruce Psaty 20, 74 Regeneron Genetics Center Kenneth Rice 20 Paul Ridker 24, 25 Simon Romaine 69 Jerome Rotter 75, 76 Perttu Salo 71 Veikko Salomaa 71 Jessica van Setten 77 Alaa Shalaby 78 Diane Smelser 47 Nicholas Smith 74, 20, 79 Steen Stender 14 David Stott 80 Per Svensson 81, 8 Mari-Liis Tammesoo 33 Kent Taylor 76 Maris Teder-Laving 82 Alexander Teumer 33, 34 Guðmundur Thorgeirsson 7, 83 Unnur Thorsteinsdóttir 7, 84 Christian Torp-Pedersen 85 Stella Trompet 52 Benoit Tyl 86 André Uitterlinden 41 Abirami Veluchamy 32 Uwe Völker 87, 34 Adriaan Voors 5 Xiaosong Wang 27 Nicholas Wareham 59 Dawn Waterworth 88 Peter Weeke 56 Raul Weiss 89 Kerri Wiggins 20 Heming Xing 27 Laura Yerges-Armstrong 88 Bing Yu 22 Faiez Zannad 90, 91, 92, 93 Jing Hua Zhao 94 Harry Hemingway 2, 95 Nilesh Samani 96 John Mcmurray 95 Jian Yang 1, 97 Peter Visscher 1, 97 Christopher Newton-Cheh 98, 99, 3 Anders Mälarstig 8, 9 Hilma Holm 7 Steven Lubitz 3, 15 Naveed Sattar 95 Michael Holmes 60, 100 Thomas Cappola 10 Folkert Asselbergs 2, 77 Aroon Hingorani 2 Karoline Kuchenbaecker 2 Patrick Ellinor 15, 3 Chim Lang 101 Kari Stefansson 7, 84 J. Gustav Smith 3, 102 Ramachandran Vasan 103, 104, 5 Daniel Swerdlow 2 R. Thomas Lumbers 2
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 herit-ability 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.
Complete list of metadata

Cited literature [95 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/hal-02577541
Contributor : Erwan Bozec <>
Submitted on : Friday, May 15, 2020 - 2:25:29 PM
Last modification on : Friday, April 2, 2021 - 3:08:35 AM

File

s41467-019-13690-5-3.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Sonia Shah, Albert Henry, Carolina Roselli, Honghuang Lin, Garðar Sveinbjörnsson, et al.. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.163. ⟨10.1038/s41467-019-13690-5⟩. ⟨hal-02577541⟩

Share

Metrics

Record views

127

Files downloads

108