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

R. Thomas Lumbers*, Sonia Shah, Regeneron Genetics Center, 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, Tõnu Esko, Mohsen Ghanbari, Isabella Kardys, Maryam Kavousi, Eliana Portilla-Fernandez, Alexander Teumer, Andre G. Uitterlinden, Jian Yang*, RS Vasan, JG Smith

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Pages (from-to)5531-5541
Number of pages11
JournalESC heart failure
Volume8
Issue number6
Early online date3 Sep 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical 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 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.

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