The genomics of heart failure: design and rationale of the HERMES consortium

Regeneron Genetics Center; R. Thomas Lumbers; Sonia Shah; Honghuang Lin; Tomasz Czuba; Albert Henry; Daniel I. Swerdlow; Anders Mälarstig; Charlotte Andersson; Niek Verweij; Michael V. Holmes; Johan Ärnlöv; Per Svensson; Harry Hemingway; Neneh Sallah; Peter Almgren; Krishna G Aragam; Geraldine Asselin; Joshua D. Backman; Mary L. Biggs; Heather L. Bloom; Eric Boersma; Jeffrey Brandimarto; Michael R. Brown; Hans-Peter Brunner-La Rocca; David J. Carey; Mark D. Chaffin; Daniel I Chasman; Olympe Chazara; Xing Chen; Xu Chen; Jonathan H Chung; William Chutkow; John G. F. Cleland; James P. Cook; Simon de Denus; Abbas Dehghan; Graciela E. Delgado; Spiros Denaxas; Alexander S. Doney; Marcus Dörr; Samuel C. Dudley; Gunnar Engström; John J. V. McMurray; Ify R. Mordi; Andrew D. Morris; Andrew P. Morris; Colin N. A. Palmer; Nicholas L. Smith; Abirami Veluchamy; Chim C. Lang; J. Gustav Smith

doi:10.1002/ehf2.13517

The genomics of heart failure: design and rationale of the HERMES consortium

Regeneron Genetics Center, R. Thomas Lumbers (Lead / Corresponding author), Sonia Shah, Honghuang Lin, Tomasz Czuba, Albert Henry, Daniel I. Swerdlow, Anders Mälarstig, Charlotte Andersson, Niek Verweij, Michael V. Holmes, Johan Ärnlöv, Per Svensson, Harry Hemingway, Neneh Sallah, Peter Almgren, Krishna G Aragam, Geraldine Asselin, Joshua D. Backman, Mary L. BiggsHeather L. Bloom, Eric Boersma, Jeffrey Brandimarto, Michael R. Brown, Hans-Peter Brunner-La Rocca, David J. Carey, Mark D. Chaffin, Daniel I Chasman, Olympe Chazara, Xing Chen, Xu Chen, Jonathan H Chung, William Chutkow, John G. F. Cleland, James P. Cook, Simon de Denus, Abbas Dehghan, Graciela E. Delgado, Spiros Denaxas, Alexander S. Doney, Marcus Dörr, Samuel C. Dudley, Gunnar Engström, John J. V. McMurray, Ify R. Mordi, Andrew D. Morris, Andrew P. Morris, Colin N. A. Palmer, Nicholas L. Smith, Abirami Veluchamy, Chim C. Lang, J. Gustav Smith (Lead / Corresponding author)

Population Health and Genomics

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

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Abstract

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.

Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

Original language	English
Pages (from-to)	5531-5541
Number of pages	11
Journal	ESC Heart Failure
Volume	8
Issue number	6
Early online date	3 Sept 2021
DOIs	https://doi.org/10.1002/ehf2.13517 https://doi.org/10.1002/ehf2.13517
Publication status	Published - Dec 2021

Keywords

Association studies
Biomarkers
Cardiomyopathy
Genetics
Heart failure

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1002/ehf2.13517Licence: CC BY-NC
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Regeneron Genetics Center, Lumbers, R. T., Shah, S., Lin, H., Czuba, T., Henry, A., Swerdlow, D. I., Mälarstig, A., Andersson, C., Verweij, N., Holmes, M. V., Ärnlöv, J., Svensson, P., Hemingway, H., Sallah, N., Almgren, P., Aragam, K. G., Asselin, G., Backman, J. D., ... Smith, J. G. (2021). The genomics of heart failure: design and rationale of the HERMES consortium. ESC Heart Failure, 8(6), 5531-5541. https://doi.org/10.1002/ehf2.13517, https://doi.org/10.1002/ehf2.13517

@article{a675d3e919ee4dbfb4c296180706f009,

title = "The genomics of heart failure: design and rationale of the HERMES consortium",

abstract = "Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.",

keywords = "Association studies, Biomarkers, Cardiomyopathy, Genetics, Heart failure",

author = "{Regeneron Genetics Center} and Lumbers, {R. Thomas} and Sonia Shah and Honghuang Lin and Tomasz Czuba and Albert Henry and Swerdlow, {Daniel I.} and Anders M{\"a}larstig and Charlotte Andersson and Niek Verweij and Holmes, {Michael V.} and Johan {\"A}rnl{\"o}v and Per Svensson and Harry Hemingway and Neneh Sallah and Peter Almgren and Aragam, {Krishna G} and Geraldine Asselin and Backman, {Joshua D.} and Biggs, {Mary L.} and Bloom, {Heather L.} and Eric Boersma and Jeffrey Brandimarto and Brown, {Michael R.} and {Brunner-La Rocca}, Hans-Peter and Carey, {David J.} and Chaffin, {Mark D.} and Chasman, {Daniel I} and Olympe Chazara and Xing Chen and Xu Chen and Chung, {Jonathan H} and William Chutkow and Cleland, {John G. F.} and Cook, {James P.} and {de Denus}, Simon and Abbas Dehghan and Delgado, {Graciela E.} and Spiros Denaxas and Doney, {Alexander S.} and Marcus D{\"o}rr and Dudley, {Samuel C.} and Gunnar Engstr{\"o}m and McMurray, {John J. V.} and Mordi, {Ify R.} and Morris, {Andrew D.} and Morris, {Andrew P.} and Palmer, {Colin N. A.} and Smith, {Nicholas L.} and Abirami Veluchamy and Lang, {Chim C.} and Smith, {J. Gustav}",

note = "Swedish Foundation for Strategic Research. Grant Number: IRC15-0067 Knut and Alice Wallenberg Foundation Swedish National Health Service Sk{\aa}ne University Hospital Crafoord Foundation European Research Council. Grant Number: ERC-STG-2015-679242 Swedish Research Council. Grant Numbers: 2009-1039, 349-2006-237, 2017-02554 Swedish Heart-Lung Foundation. Grant Numbers: 2019-0526, 2016-0315, 2016-0134 Department of Medicine, Boston University School of Medicine Evans Medical Foundation Framingham Heart Study (FHS). Grant Numbers: 75N92019D00031, HHSN268201500001I, NO1-HC-25195 American Heart Association. Grant Number: 18SFRN34250007 National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC). Grant Number: DK063491 National Center for Advancing Translational Sciences. Grant Number: UL1TR001881 British Heart Foundation Centre of Research Excellence. Grant Number: RE/18/6/34217 British Heart Foundation Cardiovascular Biomedicine National Institutes of Health. Grant Numbers: 1R01HL139731, U10 HL110337, U10 HL110336, U10 HL110302, U10 HL110312, U10 HL110338, U10 HL110262, U10 HL110309, U10 HL110342, U10 HL110297, U10 HL084904 EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart. Grant Number: 116074 NIHR UCLH Biomedical Research Centre Health Data Research UK. Grant Number: MR/S003754/1 {\textcopyright} 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2021",

month = dec,

doi = "10.1002/ehf2.13517",

language = "English",

volume = "8",

pages = "5531--5541",

journal = "ESC Heart Failure",

issn = "2055-5822",

publisher = "Wiley",

number = "6",

}

Regeneron Genetics Center, Lumbers, RT, Shah, S, Lin, H, Czuba, T, Henry, A, Swerdlow, DI, Mälarstig, A, Andersson, C, Verweij, N, Holmes, MV, Ärnlöv, J, Svensson, P, Hemingway, H, Sallah, N, Almgren, P, Aragam, KG, Asselin, G, Backman, JD, Biggs, ML, Bloom, HL, Boersma, E, Brandimarto, J, Brown, MR, Brunner-La Rocca, H-P, Carey, DJ, Chaffin, MD, Chasman, DI, Chazara, O, Chen, X, Chen, X, Chung, JH, Chutkow, W, Cleland, JGF, Cook, JP, de Denus, S, Dehghan, A, Delgado, GE, Denaxas, S, Doney, AS, Dörr, M, Dudley, SC, Engström, G, McMurray, JJV, Mordi, IR, Morris, AD, Morris, AP, Palmer, CNA, Smith, NL, Veluchamy, A , Lang, CC & Smith, JG 2021, 'The genomics of heart failure: design and rationale of the HERMES consortium', ESC Heart Failure, vol. 8, no. 6, pp. 5531-5541. https://doi.org/10.1002/ehf2.13517, https://doi.org/10.1002/ehf2.13517

TY - JOUR

T1 - The genomics of heart failure

T2 - design and rationale of the HERMES consortium

AU - Regeneron Genetics Center

AU - Lumbers, R. Thomas

AU - Shah, Sonia

AU - Lin, Honghuang

AU - Czuba, Tomasz

AU - Henry, Albert

AU - Swerdlow, Daniel I.

AU - Mälarstig, Anders

AU - Andersson, Charlotte

AU - Verweij, Niek

AU - Holmes, Michael V.

AU - Ärnlöv, Johan

AU - Svensson, Per

AU - Hemingway, Harry

AU - Sallah, Neneh

AU - Almgren, Peter

AU - Aragam, Krishna G

AU - Asselin, Geraldine

AU - Backman, Joshua D.

AU - Biggs, Mary L.

AU - Bloom, Heather L.

AU - Boersma, Eric

AU - Brandimarto, Jeffrey

AU - Brown, Michael R.

AU - Brunner-La Rocca, Hans-Peter

AU - Carey, David J.

AU - Chaffin, Mark D.

AU - Chasman, Daniel I

AU - Chazara, Olympe

AU - Chen, Xing

AU - Chen, Xu

AU - Chung, Jonathan H

AU - Chutkow, William

AU - Cleland, John G. F.

AU - Cook, James P.

AU - de Denus, Simon

AU - Dehghan, Abbas

AU - Delgado, Graciela E.

AU - Denaxas, Spiros

AU - Doney, Alexander S.

AU - Dörr, Marcus

AU - Dudley, Samuel C.

AU - Engström, Gunnar

AU - McMurray, John J. V.

AU - Mordi, Ify R.

AU - Morris, Andrew D.

AU - Morris, Andrew P.

AU - Palmer, Colin N. A.

AU - Smith, Nicholas L.

AU - Veluchamy, Abirami

AU - Lang, Chim C.

AU - Smith, J. Gustav

N1 - Swedish Foundation for Strategic Research. Grant Number: IRC15-0067 Knut and Alice Wallenberg Foundation Swedish National Health Service Skåne University Hospital Crafoord Foundation European Research Council. Grant Number: ERC-STG-2015-679242 Swedish Research Council. Grant Numbers: 2009-1039, 349-2006-237, 2017-02554 Swedish Heart-Lung Foundation. Grant Numbers: 2019-0526, 2016-0315, 2016-0134 Department of Medicine, Boston University School of Medicine Evans Medical Foundation Framingham Heart Study (FHS). Grant Numbers: 75N92019D00031, HHSN268201500001I, NO1-HC-25195 American Heart Association. Grant Number: 18SFRN34250007 National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC). Grant Number: DK063491 National Center for Advancing Translational Sciences. Grant Number: UL1TR001881 British Heart Foundation Centre of Research Excellence. Grant Number: RE/18/6/34217 British Heart Foundation Cardiovascular Biomedicine National Institutes of Health. Grant Numbers: 1R01HL139731, U10 HL110337, U10 HL110336, U10 HL110302, U10 HL110312, U10 HL110338, U10 HL110262, U10 HL110309, U10 HL110342, U10 HL110297, U10 HL084904 EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart. Grant Number: 116074 NIHR UCLH Biomedical Research Centre Health Data Research UK. Grant Number: MR/S003754/1 © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

PY - 2021/12

Y1 - 2021/12

N2 - Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

AB - Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

KW - Association studies

KW - Biomarkers

KW - Cardiomyopathy

KW - Genetics

KW - Heart failure

UR - http://www.scopus.com/inward/record.url?scp=85114632006&partnerID=8YFLogxK

U2 - 10.1002/ehf2.13517

DO - 10.1002/ehf2.13517

M3 - Article

C2 - 34480422

SN - 2055-5822

VL - 8

SP - 5531

EP - 5541

JO - ESC Heart Failure

JF - ESC Heart Failure

IS - 6

ER -

The genomics of heart failure: design and rationale of the HERMES consortium

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