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

R.T. Lumbers; S. Shah; H.H. Lin; T. Czuba; A. Henry; D.I. Swerdlow; A. Malarstig; C. Andersson; N. Verweij; M.V. Holmes; J. Arnlov; P. Svensson; H. Hemingway; N. Sallah; P. Almgren; K.G. Aragam; G. Asselin; J.D. Backman; M.L. Biggs; H.L. Bloom; E. Boersma; J. Brandimarto; M.R. Brown; H.P. Brunner-La Rocca; D.J. Carey; M.D. Chaffin; D.I. Chasman; O. Chazara; X. Chen; J.H. Chung; W. Chutkow; J.G.F. Cleland; J.P. Cook; S. de Denus; A. Dehghan; G.E. Delgado; S. Denaxas; A.S. Doney; M. Dorr; S.C. Dudley; G. Engstrom; T. Esko; G. Fatemifar; S.B. Felix; C. Finan; I. Ford; F. Fougerousse; R. Fouodjio; M. Ghanbari; Regeneron Genetics Ctr

doi:10.1002/ehf2.13517

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

R.T. Lumbers^*, S. Shah, H.H. Lin, T. Czuba, A. Henry, D.I. Swerdlow, A. Malarstig, C. Andersson, N. Verweij, M.V. Holmes, J. Arnlov, P. Svensson, H. Hemingway, N. Sallah, P. Almgren, K.G. Aragam, G. Asselin, J.D. Backman, M.L. Biggs, H.L. BloomE. Boersma, J. Brandimarto, M.R. Brown, H.P. Brunner-La Rocca, D.J. Carey, M.D. Chaffin, D.I. Chasman, O. Chazara, X. Chen, J.H. Chung, W. Chutkow, J.G.F. Cleland, J.P. Cook, S. de Denus, A. Dehghan, G.E. Delgado, S. Denaxas, A.S. Doney, M. Dorr, S.C. Dudley, G. Engstrom, T. Esko, G. Fatemifar, S.B. Felix, C. Finan, I. Ford, F. Fougerousse, R. Fouodjio, M. Ghanbari, Regeneron Genetics Ctr

^*Corresponding author for this work

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

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 x 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
Publication status	Published - Dec 2021

Keywords

Heart failure
Cardiomyopathy
Genetics
Biomarkers
Association studies
WIDE ASSOCIATION
AFRICAN ANCESTRY
AGING RESEARCH
EPIDEMIOLOGY
METAANALYSIS
CLASSIFICATION
REPLICATION
COHORTS
ADULTS
RISK

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10.1002/ehf2.13517Licence: CC BY

Cite this

Lumbers, R. T., Shah, S., Lin, H. H., Czuba, T., Henry, A., Swerdlow, D. I., Malarstig, A., Andersson, C., Verweij, N., Holmes, M. V., Arnlov, J., Svensson, P., Hemingway, H., Sallah, N., Almgren, P., Aragam, K. G., Asselin, G., Backman, J. D., Biggs, M. L., ... Regeneron Genetics Ctr (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

@article{ab36ff14dc5444198fd21e521f2b90da,

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 x 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 = "Heart failure, Cardiomyopathy, Genetics, Biomarkers, Association studies, WIDE ASSOCIATION, AFRICAN ANCESTRY, AGING RESEARCH, EPIDEMIOLOGY, METAANALYSIS, CLASSIFICATION, REPLICATION, COHORTS, ADULTS, RISK",

author = "R.T. Lumbers and S. Shah and H.H. Lin and T. Czuba and A. Henry and D.I. Swerdlow and A. Malarstig and C. Andersson and N. Verweij and M.V. Holmes and J. Arnlov and P. Svensson and H. Hemingway and N. Sallah and P. Almgren and K.G. Aragam and G. Asselin and J.D. Backman and M.L. Biggs and H.L. Bloom and E. Boersma and J. Brandimarto and M.R. Brown and {Brunner-La Rocca}, H.P. and D.J. Carey and M.D. Chaffin and D.I. Chasman and O. Chazara and X. Chen and J.H. Chung and W. Chutkow and J.G.F. Cleland and J.P. Cook and {de Denus}, S. and A. Dehghan and G.E. Delgado and S. Denaxas and A.S. Doney and M. Dorr and S.C. Dudley and G. Engstrom and T. Esko and G. Fatemifar and S.B. Felix and C. Finan and I. Ford and F. Fougerousse and R. Fouodjio and M. Ghanbari and {Regeneron Genetics Ctr}",

note = "Funding Information: R. Thomas Lumbers is supported by a UKRI Rutherford Fellowship hosted by Health Data Research UK (MR/S003754/1), the NIHR UCLH Biomedical Research Centre, and the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074. The Heart Failure Clinical Research Network and the research reported in this article were supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) under award U10 HL084904 (for the Coordinating Center) and awards U10 HL110297, U10 HL110342, U10 HL110309, U10 HL110262, U10 HL110338, U10 HL110312, U10 HL110302, U10 HL110336, and U10 HL110337 (for Regional Clinical Centers). Albert Henry is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. Simon de Denus holds the Universit{\'e} de Montr{\'e}al Chair in Pharmacogenomics. John J.V. McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Jerome I. Rotter was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Jean‐Claude Tardif holds the Canada Research Chair in Personalized Medicine and the Universit{\'e} de Montr{\'e}al Pfizer‐endowed research chair in atherosclerosis. Kent D. Taylor is supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Harvey D. White reports grants from National Heart, Lung, and Blood Institute. Steven A. Lubitz is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. Marie‐Pierre Dub{\'e} holds the Canada Research Chair in Precision medicine data analysis. Ramachandran S. Vasan acknowledges the support of contracts for the Framingham Heart Study (FHS) NO1‐HC‐25195, HHSN268201500001I, and 75N92019D00031 from the National Heart, Lung, and Blood Institute. He is also supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. J. Gustav Smith was supported by grants from the Swedish Heart‐Lung Foundation (2016‐0134, 2016‐0315, and 2019‐0526), the Swedish Research Council (2017‐02554), the EuropeanResearch Council (ERC‐STG‐2015‐679242), the Crafoord Foundation, Sk{\aa}ne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg Foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349‐2006‐237, Strategic Research Area Exodiab Dnr 2009‐1039) and Swedish Foundation for Strategic Research (Dnr IRC15‐0067) to the Lund University Diabetes Center. Funding Information: Daniel I. Swerdlow is an employee of Silence Therapeutics plc. Joshua D. Backman and Jonathan H. Chung are employees of Regeneron Genetics Center. Simon de Denus was supported through grants from Pfizer, AstraZeneca, Roche Molecular Science, DalCor, and Novartis. Bruce M. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Carolina Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. Jean‐Claude Tardif has received research support from Amarin, AstraZeneca, DalCor, Ionis, Pfizer, RegenexBio, Sanofi, and Servier and honoraria from AstraZeneca, DalCor, Pfizer, Sanofi, and Servier; holds minor equity interest in DalCor; and is an author of a patent on pharmacogenomics‐guided CETP inhibition. Benoit Tyl receives full‐time salary from Servier. Harvey D. White reports grants and personal fees from Eli Lilly and Company, Omthera Pharmaceuticals, Pfizer USA, Eisai Inc., DalCor Pharma UK Inc, CSL Behring LLC, American Regent, Sanofi‐Aventis Australia Pty Ltd, and Esperion Therapeutics Inc. and personal fees from Genentech, Inc., outside the submitted work. Steven A. Lubitz receives sponsored research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, and Fitbit and has consulted for Bristol Myers Squibb/Pfizer and Bayer AG. Michael E. Dunn is an employee of Regeneron Pharmaceuticals. Marie‐Pierre Dub{\'e} has received honoraria from Dalcor, holds minor equity interest in DalCor, is an author of a patent on pharmacogenomics‐guided CETP inhibition, and has received research support (access to samples and data) from AstraZeneca, Pfizer, Servier, Sanofi, and GlaxoSmithKline. Authors affiliated with deCODE genetics are employed by deCODE genetics/Amgen Inc. Publisher Copyright: {\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 = "John Wiley & Sons Inc.",

number = "6",

}

Lumbers, RT, Shah, S, Lin, HH, Czuba, T, Henry, A, Swerdlow, DI, Malarstig, A, Andersson, C, Verweij, N, Holmes, MV, Arnlov, 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, HP, Carey, DJ, Chaffin, MD, Chasman, DI, Chazara, O, Chen, X, Chung, JH, Chutkow, W, Cleland, JGF, Cook, JP, de Denus, S, Dehghan, A, Delgado, GE, Denaxas, S, Doney, AS, Dorr, M, Dudley, SC, Engstrom, G, Esko, T, Fatemifar, G, Felix, SB, Finan, C, Ford, I, Fougerousse, F, Fouodjio, R, Ghanbari, M & Regeneron Genetics Ctr 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

TY - JOUR

T1 - The genomics of heart failure: design and rationale of the HERMES consortium

AU - Lumbers, R.T.

AU - Shah, S.

AU - Lin, H.H.

AU - Czuba, T.

AU - Henry, A.

AU - Swerdlow, D.I.

AU - Malarstig, A.

AU - Andersson, C.

AU - Verweij, N.

AU - Holmes, M.V.

AU - Arnlov, J.

AU - Svensson, P.

AU - Hemingway, H.

AU - Sallah, N.

AU - Almgren, P.

AU - Aragam, K.G.

AU - Asselin, G.

AU - Backman, J.D.

AU - Biggs, M.L.

AU - Bloom, H.L.

AU - Boersma, E.

AU - Brandimarto, J.

AU - Brown, M.R.

AU - Brunner-La Rocca, H.P.

AU - Carey, D.J.

AU - Chaffin, M.D.

AU - Chasman, D.I.

AU - Chazara, O.

AU - Chen, X.

AU - Chung, J.H.

AU - Chutkow, W.

AU - Cleland, J.G.F.

AU - Cook, J.P.

AU - de Denus, S.

AU - Dehghan, A.

AU - Delgado, G.E.

AU - Denaxas, S.

AU - Doney, A.S.

AU - Dorr, M.

AU - Dudley, S.C.

AU - Engstrom, G.

AU - Esko, T.

AU - Fatemifar, G.

AU - Felix, S.B.

AU - Finan, C.

AU - Ford, I.

AU - Fougerousse, F.

AU - Fouodjio, R.

AU - Ghanbari, M.

AU - Regeneron Genetics Ctr

N1 - Funding Information: R. Thomas Lumbers is supported by a UKRI Rutherford Fellowship hosted by Health Data Research UK (MR/S003754/1), the NIHR UCLH Biomedical Research Centre, and the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074. The Heart Failure Clinical Research Network and the research reported in this article were supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) under award U10 HL084904 (for the Coordinating Center) and awards U10 HL110297, U10 HL110342, U10 HL110309, U10 HL110262, U10 HL110338, U10 HL110312, U10 HL110302, U10 HL110336, and U10 HL110337 (for Regional Clinical Centers). Albert Henry is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. Simon de Denus holds the Université de Montréal Chair in Pharmacogenomics. John J.V. McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Jerome I. Rotter was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Jean‐Claude Tardif holds the Canada Research Chair in Personalized Medicine and the Université de Montréal Pfizer‐endowed research chair in atherosclerosis. Kent D. Taylor is supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Harvey D. White reports grants from National Heart, Lung, and Blood Institute. Steven A. Lubitz is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. Marie‐Pierre Dubé holds the Canada Research Chair in Precision medicine data analysis. Ramachandran S. Vasan acknowledges the support of contracts for the Framingham Heart Study (FHS) NO1‐HC‐25195, HHSN268201500001I, and 75N92019D00031 from the National Heart, Lung, and Blood Institute. He is also supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. J. Gustav Smith was supported by grants from the Swedish Heart‐Lung Foundation (2016‐0134, 2016‐0315, and 2019‐0526), the Swedish Research Council (2017‐02554), the EuropeanResearch Council (ERC‐STG‐2015‐679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg Foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349‐2006‐237, Strategic Research Area Exodiab Dnr 2009‐1039) and Swedish Foundation for Strategic Research (Dnr IRC15‐0067) to the Lund University Diabetes Center. Funding Information: Daniel I. Swerdlow is an employee of Silence Therapeutics plc. Joshua D. Backman and Jonathan H. Chung are employees of Regeneron Genetics Center. Simon de Denus was supported through grants from Pfizer, AstraZeneca, Roche Molecular Science, DalCor, and Novartis. Bruce M. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Carolina Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. Jean‐Claude Tardif has received research support from Amarin, AstraZeneca, DalCor, Ionis, Pfizer, RegenexBio, Sanofi, and Servier and honoraria from AstraZeneca, DalCor, Pfizer, Sanofi, and Servier; holds minor equity interest in DalCor; and is an author of a patent on pharmacogenomics‐guided CETP inhibition. Benoit Tyl receives full‐time salary from Servier. Harvey D. White reports grants and personal fees from Eli Lilly and Company, Omthera Pharmaceuticals, Pfizer USA, Eisai Inc., DalCor Pharma UK Inc, CSL Behring LLC, American Regent, Sanofi‐Aventis Australia Pty Ltd, and Esperion Therapeutics Inc. and personal fees from Genentech, Inc., outside the submitted work. Steven A. Lubitz receives sponsored research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, and Fitbit and has consulted for Bristol Myers Squibb/Pfizer and Bayer AG. Michael E. Dunn is an employee of Regeneron Pharmaceuticals. Marie‐Pierre Dubé has received honoraria from Dalcor, holds minor equity interest in DalCor, is an author of a patent on pharmacogenomics‐guided CETP inhibition, and has received research support (access to samples and data) from AstraZeneca, Pfizer, Servier, Sanofi, and GlaxoSmithKline. Authors affiliated with deCODE genetics are employed by deCODE genetics/Amgen Inc. Publisher Copyright: © 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 x 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 x 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 - Heart failure

KW - Cardiomyopathy

KW - Genetics

KW - Biomarkers

KW - Association studies

KW - WIDE ASSOCIATION

KW - AFRICAN ANCESTRY

KW - AGING RESEARCH

KW - EPIDEMIOLOGY

KW - METAANALYSIS

KW - CLASSIFICATION

KW - REPLICATION

KW - COHORTS

KW - ADULTS

KW - RISK

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 -