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

Sonia Shah; Daniel Gudbjartsson; Unnur Thorsteinsdottir; Kari Stefansson; Albert Henry; Carolina Roselli; Honghuang Lin; Garðar Sveinbjörnsson; Ghazaleh Fatemifar; Åsa K Hedman; Jemma B Wilk; Michael P Morley; Mark D Chaffin; Anna Helgadottir; Niek Verweij; Abbas Dehghan; Peter Almgren; Charlotte Andersson; Krishna G Aragam; Johan Ärnlöv; Joshua D Backman; Mary L Biggs; Heather L Bloom; Jeffrey Brandimarto; Michael R Brown; Leonard Buckbinder; David J Carey; Daniel I Chasman; Xing Chen; Xu Chen; Jonathan Chung; William Chutkow; James P Cook; Graciela E Delgado; Spiros Denaxas; Alexander S Doney; Marcus Dörr; Samuel C Dudley; Michael E Dunn; Gunnar Engström; Tõnu Esko; Stephan B Felix; Chris Finan; Ian Ford; Mohsen Ghanbari; Sahar Ghasemi; Vilmantas Giedraitis; Franco Giulianini; John S Gottdiener; Stefan Gross; Daníel F Guðbjartsson; Rebecca Gutmann; Christopher M Haggerty; Pim van der Harst; Craig L Hyde; Erik Ingelsson; J Wouter Jukema; Maryam Kavousi; Kay-Tee Khaw; Marcus E Kleber; Lars Køber; Andrea Koekemoer; Claudia Langenberg; Lars Lind; Cecilia M Lindgren; Barry London; Luca A Lotta; Ruth C Lovering; Jian'an Luan; Patrik Magnusson; Anubha Mahajan; Kenneth B Margulies; Winfried März; Olle Melander; Ify R Mordi; Thomas Morgan; Andrew D Morris; Andrew P Morris; Alanna C Morrison; Michael W Nagle; Christopher P Nelson; Alexander Niessner; Teemu Niiranen; Michelle L O'Donoghue; Anjali T Owens; Colin N A Palmer; Helen M Parry; Markus Perola; Eliana Portilla-Fernandez; Bruce M Psaty; Kenneth M Rice; Paul M Ridker; Simon P R Romaine; Jerome I Rotter; Perttu Salo; Veikko Salomaa; Jessica van Setten; Alaa A Shalaby; Diane T Smelser; Nicholas L Smith; Steen Stender; David J Stott; Per Svensson; Mari-Liis Tammesoo; Kent D Taylor; Maris Teder-Laving; Alexander Teumer; Guðmundur Thorgeirsson; Christian Torp-Pedersen; Stella Trompet; Benoit Tyl; Andre G Uitterlinden; Abirami Veluchamy; Uwe Völker; Adriaan A Voors; Xiaosong Wang; Nicholas J Wareham; Dawn Waterworth; Peter E Weeke; Raul Weiss; Kerri L Wiggins; Heming Xing; Laura M Yerges-Armstrong; Bing Yu; Faiez Zannad; Jing Hua Zhao; Harry Hemingway; Nilesh J Samani; John J V McMurray; Jian Yang; Peter M Visscher; Christopher Newton-Cheh; Anders Malarstig; Hilma Holm; Steven A Lubitz; Naveed Sattar; Michael V Holmes; Thomas P Cappola; Folkert W Asselbergs; Aroon D Hingorani; Karoline Kuchenbaecker; Patrick T Ellinor; Chim C Lang; J Gustav Smith; Ramachandran S Vasan; Daniel I Swerdlow; R Thomas Lumbers

doi:10.1038/s41467-019-13690-5

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

Sonia Shah, Daniel Gudbjartsson, Unnur Thorsteinsdottir, Kari Stefansson, Albert Henry, Carolina Roselli, Honghuang Lin, Garðar Sveinbjörnsson, Ghazaleh Fatemifar, Åsa K Hedman, Jemma B Wilk, Michael P Morley, Mark D Chaffin, Anna Helgadottir, Niek Verweij, Abbas Dehghan, Peter Almgren, Charlotte Andersson, Krishna G Aragam, Johan ÄrnlövJoshua D Backman, Mary L Biggs, Heather L Bloom, Jeffrey Brandimarto, Michael R Brown, Leonard Buckbinder, David J Carey, Daniel I Chasman, Xing Chen, Xu Chen, Jonathan Chung, William Chutkow, James P Cook, Graciela E Delgado, Spiros Denaxas, Alexander S Doney, Marcus Dörr, Samuel C Dudley, Michael E Dunn, Gunnar Engström, Tõnu Esko, Stephan B Felix, Chris Finan, Ian Ford, Mohsen Ghanbari, Sahar Ghasemi, Vilmantas Giedraitis, Franco Giulianini, John S Gottdiener, Stefan Gross, Daníel F Guðbjartsson, Rebecca Gutmann, Christopher M Haggerty, Pim van der Harst, Craig L Hyde, Erik Ingelsson, J Wouter Jukema, Maryam Kavousi, Kay-Tee Khaw, Marcus E Kleber, Lars Køber, Andrea Koekemoer, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Barry London, Luca A Lotta, Ruth C Lovering, Jian'an Luan, Patrik Magnusson, Anubha Mahajan, Kenneth B Margulies, Winfried März, Olle Melander, Ify R Mordi, Thomas Morgan, Andrew D Morris, Andrew P Morris, Alanna C Morrison, Michael W Nagle, Christopher P Nelson, Alexander Niessner, Teemu Niiranen, Michelle L O'Donoghue, Anjali T Owens, Colin N A Palmer, Helen M Parry, Markus Perola, Eliana Portilla-Fernandez, Bruce M Psaty, Kenneth M Rice, Paul M Ridker, Simon P R Romaine, Jerome I Rotter, Perttu Salo, Veikko Salomaa, Jessica van Setten, Alaa A Shalaby, Diane T Smelser, Nicholas L Smith, Steen Stender, David J Stott, Per Svensson, Mari-Liis Tammesoo, Kent D Taylor, Maris Teder-Laving, Alexander Teumer, Guðmundur Thorgeirsson, Christian Torp-Pedersen, Stella Trompet, Benoit Tyl, Andre G Uitterlinden, Abirami Veluchamy, Uwe Völker, Adriaan A Voors, Xiaosong Wang, Nicholas J Wareham, Dawn Waterworth, Peter E Weeke, Raul Weiss, Kerri L Wiggins, Heming Xing, Laura M Yerges-Armstrong, Bing Yu, Faiez Zannad, Jing Hua Zhao, Harry Hemingway, Nilesh J Samani, John J V McMurray, Jian Yang, Peter M Visscher, Christopher Newton-Cheh, Anders Malarstig, Hilma Holm, Steven A Lubitz, Naveed Sattar, Michael V Holmes, Thomas P Cappola, Folkert W Asselbergs, Aroon D Hingorani, Karoline Kuchenbaecker, Patrick T Ellinor, Chim C Lang, J Gustav Smith, Ramachandran S Vasan, Daniel I Swerdlow, R Thomas Lumbers

University of Iceland

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	163
Number of pages	163
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13690-5
Publication status	Published - 9 Jan 2020

Other keywords

Blóðrásarsjúkdómar
Dánartíðni
Erfðarannsóknir
Gen
Genome-Wide Association Study
Heart failure
Hjartabilun
Morbidity
Mortality

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-13690-5

Cite this

Shah, S., Gudbjartsson, D., Thorsteinsdottir, U., Stefansson, K., Henry, A., Roselli, C., Lin, H., Sveinbjörnsson, G., Fatemifar, G., Hedman, Å. K., Wilk, J. B., Morley, M. P., Chaffin, M. D., Helgadottir, A., Verweij, N., Dehghan, A., Almgren, P., Andersson, C., Aragam, K. G., ... Lumbers, R. T. (2020). Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications, 11(1), 163. https://doi.org/10.1038/s41467-019-13690-5

@article{7caec6b372ab4a269548a69538802550,

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

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.",

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author = "Sonia Shah and Daniel Gudbjartsson and Unnur Thorsteinsdottir and Kari Stefansson and Albert Henry and Carolina Roselli and Honghuang Lin and Gar{\dh}ar Sveinbj{\"o}rnsson and Ghazaleh Fatemifar and Hedman, \{{\AA}sa K\} and Wilk, \{Jemma B\} and Morley, \{Michael P\} and Chaffin, \{Mark D\} and Anna Helgadottir and Niek Verweij and Abbas Dehghan and Peter Almgren and Charlotte Andersson and Aragam, \{Krishna G\} and Johan {\"A}rnl{\"o}v and Backman, \{Joshua D\} and Biggs, \{Mary L\} and Bloom, \{Heather L\} and Jeffrey Brandimarto and Brown, \{Michael R\} and Leonard Buckbinder and Carey, \{David J\} and Chasman, \{Daniel I\} and Xing Chen and Xu Chen and Jonathan Chung and William Chutkow and Cook, \{James P\} and Delgado, \{Graciela E\} and Spiros Denaxas and Doney, \{Alexander S\} and Marcus D{\"o}rr and Dudley, \{Samuel C\} and Dunn, \{Michael E\} and Gunnar Engstr{\"o}m and T{\~o}nu Esko and Felix, \{Stephan B\} and Chris Finan and Ian Ford and Mohsen Ghanbari and Sahar Ghasemi and Vilmantas Giedraitis and Franco Giulianini and Gottdiener, \{John S\} and Stefan Gross and Gu{\dh}bjartsson, \{Dan{\'i}el F\} and Rebecca Gutmann and Haggerty, \{Christopher M\} and \{van der Harst\}, Pim and Hyde, \{Craig L\} and Erik Ingelsson and Jukema, \{J Wouter\} and Maryam Kavousi and Kay-Tee Khaw and Kleber, \{Marcus E\} and Lars K{\o}ber and Andrea Koekemoer and Claudia Langenberg and Lars Lind and Lindgren, \{Cecilia M\} and Barry London and Lotta, \{Luca A\} and Lovering, \{Ruth C\} and Jian'an Luan and Patrik Magnusson and Anubha Mahajan and Margulies, \{Kenneth B\} and Winfried M{\"a}rz and Olle Melander and Mordi, \{Ify R\} and Thomas Morgan and Morris, \{Andrew D\} and Morris, \{Andrew P\} and Morrison, \{Alanna C\} and Nagle, \{Michael W\} and Nelson, \{Christopher P\} and Alexander Niessner and Teemu Niiranen and O'Donoghue, \{Michelle L\} and Owens, \{Anjali T\} and Palmer, \{Colin N A\} and Parry, \{Helen M\} and Markus Perola and Eliana Portilla-Fernandez and Psaty, \{Bruce M\} and Rice, \{Kenneth M\} and Ridker, \{Paul M\} and Romaine, \{Simon P R\} and Rotter, \{Jerome I\} and Perttu Salo and Veikko Salomaa and \{van Setten\}, Jessica and Shalaby, \{Alaa A\} and Smelser, \{Diane T\} and Smith, \{Nicholas L\} and Steen Stender and Stott, \{David J\} and Per Svensson and Mari-Liis Tammesoo and Taylor, \{Kent D\} and Maris Teder-Laving and Alexander Teumer and Gu{\dh}mundur Thorgeirsson and Christian Torp-Pedersen and Stella Trompet and Benoit Tyl and Uitterlinden, \{Andre G\} and Abirami Veluchamy and Uwe V{\"o}lker and Voors, \{Adriaan A\} and Xiaosong Wang and Wareham, \{Nicholas J\} and Dawn Waterworth and Weeke, \{Peter E\} and Raul Weiss and Wiggins, \{Kerri L\} and Heming Xing and Yerges-Armstrong, \{Laura M\} and Bing Yu and Faiez Zannad and Zhao, \{Jing Hua\} and Harry Hemingway and Samani, \{Nilesh J\} and McMurray, \{John J V\} and Jian Yang and Visscher, \{Peter M\} and Christopher Newton-Cheh and Anders Malarstig and Hilma Holm and Lubitz, \{Steven A\} and Naveed Sattar and Holmes, \{Michael V\} and Cappola, \{Thomas P\} and Asselbergs, \{Folkert W\} and Hingorani, \{Aroon D\} and Karoline Kuchenbaecker and Ellinor, \{Patrick T\} and Lang, \{Chim C\} and Smith, \{J Gustav\} and Vasan, \{Ramachandran S\} and Swerdlow, \{Daniel I\} and Lumbers, \{R Thomas\}",

year = "2020",

month = jan,

day = "9",

doi = "10.1038/s41467-019-13690-5",

language = "English",

volume = "11",

pages = "163",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Shah, S, Gudbjartsson, D, Thorsteinsdottir, U, Stefansson, K, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, ÅK, Wilk, JB, Morley, MP, Chaffin, MD, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, KG, Ärnlöv, J, Backman, JD, Biggs, ML, Bloom, HL, Brandimarto, J, Brown, MR, Buckbinder, L, Carey, DJ, Chasman, DI, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, JP, Delgado, GE, Denaxas, S, Doney, AS, Dörr, M, Dudley, SC, Dunn, ME, Engström, G, Esko, T, Felix, SB, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Giedraitis, V, Giulianini, F, Gottdiener, JS, Gross, S, Guðbjartsson, DF, Gutmann, R, Haggerty, CM, van der Harst, P, Hyde, CL, Ingelsson, E, Jukema, JW, Kavousi, M, Khaw, K-T, Kleber, ME, Køber, L, Koekemoer, A, Langenberg, C, Lind, L, Lindgren, CM, London, B, Lotta, LA, Lovering, RC, Luan, J, Magnusson, P, Mahajan, A, Margulies, KB, März, W, Melander, O, Mordi, IR, Morgan, T, Morris, AD, Morris, AP, Morrison, AC, Nagle, MW, Nelson, CP, Niessner, A, Niiranen, T, O'Donoghue, ML, Owens, AT, Palmer, CNA, Parry, HM, Perola, M, Portilla-Fernandez, E, Psaty, BM, Rice, KM, Ridker, PM, Romaine, SPR, Rotter, JI, Salo, P, Salomaa, V, van Setten, J, Shalaby, AA, Smelser, DT, Smith, NL, Stender, S, Stott, DJ, Svensson, P, Tammesoo, M-L, Taylor, KD, Teder-Laving, M, Teumer, A, Thorgeirsson, G, Torp-Pedersen, C, Trompet, S, Tyl, B, Uitterlinden, AG, Veluchamy, A, Völker, U, Voors, AA, Wang, X, Wareham, NJ, Waterworth, D, Weeke, PE, Weiss, R, Wiggins, KL, Xing, H, Yerges-Armstrong, LM, Yu, B, Zannad, F, Zhao, JH, Hemingway, H, Samani, NJ, McMurray, JJV, Yang, J, Visscher, PM, Newton-Cheh, C, Malarstig, A, Holm, H, Lubitz, SA, Sattar, N, Holmes, MV, Cappola, TP, Asselbergs, FW, Hingorani, AD, Kuchenbaecker, K, Ellinor, PT, Lang, CC, Smith, JG, Vasan, RS, Swerdlow, DI & Lumbers, RT 2020, 'Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure', Nature Communications, vol. 11, no. 1, pp. 163. https://doi.org/10.1038/s41467-019-13690-5

TY - JOUR

T1 - Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

AU - Shah, Sonia

AU - Gudbjartsson, Daniel

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Henry, Albert

AU - Roselli, Carolina

AU - Lin, Honghuang

AU - Sveinbjörnsson, Garðar

AU - Fatemifar, Ghazaleh

AU - Hedman, Åsa K

AU - Wilk, Jemma B

AU - Morley, Michael P

AU - Chaffin, Mark D

AU - Helgadottir, Anna

AU - Verweij, Niek

AU - Dehghan, Abbas

AU - Almgren, Peter

AU - Andersson, Charlotte

AU - Aragam, Krishna G

AU - Ärnlöv, Johan

AU - Backman, Joshua D

AU - Biggs, Mary L

AU - Bloom, Heather L

AU - Brandimarto, Jeffrey

AU - Brown, Michael R

AU - Buckbinder, Leonard

AU - Carey, David J

AU - Chasman, Daniel I

AU - Chen, Xing

AU - Chen, Xu

AU - Chung, Jonathan

AU - Chutkow, William

AU - Cook, James P

AU - Delgado, Graciela E

AU - Denaxas, Spiros

AU - Doney, Alexander S

AU - Dörr, Marcus

AU - Dudley, Samuel C

AU - Dunn, Michael E

AU - Engström, Gunnar

AU - Esko, Tõnu

AU - Felix, Stephan B

AU - Finan, Chris

AU - Ford, Ian

AU - Ghanbari, Mohsen

AU - Ghasemi, Sahar

AU - Giedraitis, Vilmantas

AU - Giulianini, Franco

AU - Gottdiener, John S

AU - Gross, Stefan

AU - Guðbjartsson, Daníel F

AU - Gutmann, Rebecca

AU - Haggerty, Christopher M

AU - van der Harst, Pim

AU - Hyde, Craig L

AU - Ingelsson, Erik

AU - Jukema, J Wouter

AU - Kavousi, Maryam

AU - Khaw, Kay-Tee

AU - Kleber, Marcus E

AU - Køber, Lars

AU - Koekemoer, Andrea

AU - Langenberg, Claudia

AU - Lind, Lars

AU - Lindgren, Cecilia M

AU - London, Barry

AU - Lotta, Luca A

AU - Lovering, Ruth C

AU - Luan, Jian'an

AU - Magnusson, Patrik

AU - Mahajan, Anubha

AU - Margulies, Kenneth B

AU - März, Winfried

AU - Melander, Olle

AU - Mordi, Ify R

AU - Morgan, Thomas

AU - Morris, Andrew D

AU - Morris, Andrew P

AU - Morrison, Alanna C

AU - Nagle, Michael W

AU - Nelson, Christopher P

AU - Niessner, Alexander

AU - Niiranen, Teemu

AU - O'Donoghue, Michelle L

AU - Owens, Anjali T

AU - Palmer, Colin N A

AU - Parry, Helen M

AU - Perola, Markus

AU - Portilla-Fernandez, Eliana

AU - Psaty, Bruce M

AU - Rice, Kenneth M

AU - Ridker, Paul M

AU - Romaine, Simon P R

AU - Rotter, Jerome I

AU - Salo, Perttu

AU - Salomaa, Veikko

AU - van Setten, Jessica

AU - Shalaby, Alaa A

AU - Smelser, Diane T

AU - Smith, Nicholas L

AU - Stender, Steen

AU - Stott, David J

AU - Svensson, Per

AU - Tammesoo, Mari-Liis

AU - Taylor, Kent D

AU - Teder-Laving, Maris

AU - Teumer, Alexander

AU - Thorgeirsson, Guðmundur

AU - Torp-Pedersen, Christian

AU - Trompet, Stella

AU - Tyl, Benoit

AU - Uitterlinden, Andre G

AU - Veluchamy, Abirami

AU - Völker, Uwe

AU - Voors, Adriaan A

AU - Wang, Xiaosong

AU - Wareham, Nicholas J

AU - Waterworth, Dawn

AU - Weeke, Peter E

AU - Weiss, Raul

AU - Wiggins, Kerri L

AU - Xing, Heming

AU - Yerges-Armstrong, Laura M

AU - Yu, Bing

AU - Zannad, Faiez

AU - Zhao, Jing Hua

AU - Hemingway, Harry

AU - Samani, Nilesh J

AU - McMurray, John J V

AU - Yang, Jian

AU - Visscher, Peter M

AU - Newton-Cheh, Christopher

AU - Malarstig, Anders

AU - Holm, Hilma

AU - Lubitz, Steven A

AU - Sattar, Naveed

AU - Holmes, Michael V

AU - Cappola, Thomas P

AU - Asselbergs, Folkert W

AU - Hingorani, Aroon D

AU - Kuchenbaecker, Karoline

AU - Ellinor, Patrick T

AU - Lang, Chim C

AU - Smith, J Gustav

AU - Vasan, Ramachandran S

AU - Swerdlow, Daniel I

AU - Lumbers, R Thomas

PY - 2020/1/9

Y1 - 2020/1/9

N2 - 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.

AB - 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.

KW - Blóðrásarsjúkdómar

KW - Dánartíðni

KW - Erfðarannsóknir

KW - Gen

KW - Genome-Wide Association Study

KW - Heart failure

KW - Hjartabilun

KW - Morbidity

KW - Mortality

KW - Blóðrásarsjúkdómar

KW - Dánartíðni

KW - Erfðarannsóknir

KW - Gen

KW - Genome-Wide Association Study

KW - Heart failure

KW - Hjartabilun

KW - Morbidity

KW - Mortality

U2 - 10.1038/s41467-019-13690-5

DO - 10.1038/s41467-019-13690-5

M3 - Article

C2 - 31919418

SN - 2041-1723

VL - 11

SP - 163

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Other keywords

UN SDGs

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