Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

EchoGen Consortium; Sonia Shah; 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; Daniel 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 K. E. Magnusson; Anubha Mahajan; Kenneth B. Margulies; Winfried März; Olle Melander; Ify Mordi; Thomas  Morgan; Andrew 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 Palmer; Helen 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; Unnur Thorsteinsdottir; Christian Torp-Pedersen; Stella Trompet; Benoit Tyl; André G. Uitterlinden; Abirami Veluchamy; Uwe Völker; Adriaan A. Voors; Xiaosong Wang; Nicholas J. Wareham; Dawn M. Waterworth; Peter E. Weeke; Raul Weiss; Kerri L. Wiggins; Heming Xing; Laura M. Yerges-Armstrong; Bing Yu; Faïez Zannad; Jing Hua Zhao; Harry Hemingway; Nilesh J. Samani; John J. V. McMurray; Jian Yang; Peter M. Visscher; Christopher Newton-Cheh; Anders Mälarstig; 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 Lang; Kari Stefansson; J. Gustav Smith; Ramachandran S. Vasan; Daniel I Swerdlow; R. Thomas Lumbers

doi:10.1101/682013

Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

, , EchoGen Consortium, Sonia Shah, 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, Daniel 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 K. E. Magnusson, Anubha Mahajan, Kenneth B. Margulies, Winfried März, Olle Melander, Ify Mordi, Thomas Morgan, Andrew 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 Palmer, Helen 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, Unnur Thorsteinsdottir, Christian Torp-Pedersen, Stella Trompet, Benoit Tyl, André G. Uitterlinden, Abirami Veluchamy, Uwe Völker, Adriaan A. Voors, Xiaosong Wang, Nicholas J. Wareham, Dawn M. Waterworth, Peter E. Weeke, Raul Weiss, Kerri L. Wiggins, Heming Xing, Laura M. Yerges-Armstrong, Bing Yu, Faïez Zannad, Jing Hua Zhao, Harry Hemingway, Nilesh J. Samani, John J. V. McMurray, Jian Yang, Peter M. Visscher, Christopher Newton-Cheh, Anders Mälarstig, 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 Lang, Kari Stefansson, J. Gustav Smith, Ramachandran S. Vasan, Daniel I Swerdlow, R. Thomas Lumbers (Lead / Corresponding author)

Research output: Working paper/Preprint › Preprint

Abstract

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.

Original language	English
Publisher	BioRxiv
Number of pages	46
DOIs	https://doi.org/10.1101/682013
Publication status	Published - 10 Jun 2019

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10.1101/682013

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, EchoGen Consortium, Shah, S., 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. (2019). Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure. BioRxiv. https://doi.org/10.1101/682013

@techreport{526e7b33f53b414f973b09587250b863,

title = "Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure",

abstract = "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.",

author = "{EchoGen Consortium} and Sonia Shah 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, {Daniel 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 Magnusson, {Patrik K. E.} and Anubha Mahajan and Margulies, {Kenneth B.} and Winfried M{\"a}rz and Olle Melander and Ify Mordi and Thomas Morgan and Andrew Morris 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 Colin Palmer and Helen Parry 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 Unnur Thorsteinsdottir and Christian Torp-Pedersen and Stella Trompet and Benoit Tyl and Uitterlinden, {Andr{\'e} G.} and Abirami Veluchamy and Uwe V{\"o}lker and Voors, {Adriaan A.} and Xiaosong Wang and Wareham, {Nicholas J.} and Waterworth, {Dawn M.} and Weeke, {Peter E.} and Raul Weiss and Wiggins, {Kerri L.} and Heming Xing and Yerges-Armstrong, {Laura M.} and Bing Yu and Fa{\"i}ez 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 M{\"a}larstig 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 Chim Lang and Kari Stefansson and Smith, {J. Gustav} and Vasan, {Ramachandran S.} and Swerdlow, {Daniel I} and Lumbers, {R. Thomas}",

note = "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.",

year = "2019",

month = jun,

day = "10",

doi = "10.1101/682013",

language = "English",

publisher = "BioRxiv",

address = "United States",

type = "WorkingPaper",

institution = "BioRxiv",

}

EchoGen Consortium, Shah, S, 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, PKE, Mahajan, A, Margulies, KB, März, W, Melander, O, Mordi, I, Morgan, T, Morris, A, Morris, AP, Morrison, AC, Nagle, MW, Nelson, CP, Niessner, A, Niiranen, T, O'Donoghue, ML, Owens, AT, Palmer, C, Parry, H, 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, Thorsteinsdottir, U, Torp-Pedersen, C, Trompet, S, Tyl, B, Uitterlinden, AG, Veluchamy, A, Völker, U, Voors, AA, Wang, X, Wareham, NJ, Waterworth, DM, 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, Mälarstig, A, Holm, H, Lubitz, SA, Sattar, N, Holmes, MV, Cappola, TP, Asselbergs, FW, Hingorani, AD, Kuchenbaecker, K, Ellinor, PT, Lang, C, Stefansson, K, Smith, JG & Vasan, RS & Swerdlow, DI & Lumbers, RT 2019 'Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure' BioRxiv. https://doi.org/10.1101/682013

TY - UNPB

T1 - Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

AU - EchoGen Consortium

AU - Shah, Sonia

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, Daniel 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 K. E.

AU - Mahajan, Anubha

AU - Margulies, Kenneth B.

AU - März, Winfried

AU - Melander, Olle

AU - Mordi, Ify

AU - Morgan, Thomas

AU - Morris, Andrew

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

AU - Parry, Helen

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 - Thorsteinsdottir, Unnur

AU - Torp-Pedersen, Christian

AU - Trompet, Stella

AU - Tyl, Benoit

AU - Uitterlinden, André G.

AU - Veluchamy, Abirami

AU - Völker, Uwe

AU - Voors, Adriaan A.

AU - Wang, Xiaosong

AU - Wareham, Nicholas J.

AU - Waterworth, Dawn M.

AU - Weeke, Peter E.

AU - Weiss, Raul

AU - Wiggins, Kerri L.

AU - Xing, Heming

AU - Yerges-Armstrong, Laura M.

AU - Yu, Bing

AU - Zannad, Faïez

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 - Mälarstig, 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

AU - Stefansson, Kari

AU - Smith, J. Gustav

AU - Vasan, Ramachandran S.

AU - Swerdlow, Daniel I

AU - Lumbers, R. Thomas

PY - 2019/6/10

Y1 - 2019/6/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85095626022&partnerID=MN8TOARS

U2 - 10.1101/682013

DO - 10.1101/682013

M3 - Preprint

BT - Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

PB - BioRxiv

ER -

Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

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