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

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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. / Shah, Sonia; Henry, 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; Køber, Lars; Regeneron Genetics Center ; Stender, Steen; Torp-Pedersen, Christian; Weeke, Peter Ejvin; Vasan, Ramachandran S; Swerdlow, Daniel I; Lumbers, R Thomas.

In: Nature Communications, Vol. 11, 163, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, Køber, L, Regeneron Genetics Center, Stender, S, Torp-Pedersen, C, Weeke, PE, 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, 163. https://doi.org/10.1038/s41467-019-13690-5

APA

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., Ärnlöv, J., Backman, J. D., Biggs, M. L., ... Lumbers, R. T. (2020). Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications, 11, [163]. https://doi.org/10.1038/s41467-019-13690-5

Vancouver

Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications. 2020;11. 163. https://doi.org/10.1038/s41467-019-13690-5

Author

Shah, Sonia ; Henry, 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 ; Køber, Lars ; Regeneron Genetics Center ; Stender, Steen ; Torp-Pedersen, Christian ; Weeke, Peter Ejvin ; Vasan, Ramachandran S ; Swerdlow, Daniel I ; Lumbers, R Thomas. / Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{0ded6740e1b84f738f64cd5af18c079c,
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.",
author = "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 Lars K{\o}ber and {Regeneron Genetics Center} and Steen Stender and Christian Torp-Pedersen and Weeke, {Peter Ejvin} and Vasan, {Ramachandran S} and Swerdlow, {Daniel I} and Lumbers, {R Thomas}",
year = "2020",
doi = "10.1038/s41467-019-13690-5",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

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

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 - Køber, Lars

AU - Regeneron Genetics Center

AU - Stender, Steen

AU - Torp-Pedersen, Christian

AU - Weeke, Peter Ejvin

AU - Vasan, Ramachandran S

AU - Swerdlow, Daniel I

AU - Lumbers, R Thomas

PY - 2020

Y1 - 2020

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.

U2 - 10.1038/s41467-019-13690-5

DO - 10.1038/s41467-019-13690-5

M3 - Journal article

C2 - 31919418

AN - SCOPUS:85077697294

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 163

ER -

ID: 256321823