The genomics of heart failure: design and rationale of the HERMES consortium
Authors: Lumbers R. Thomas , Shah Sonia , Lin Honghuang , Czuba Tomasz , Henry Albert , Swerdlow Daniel I. , Mälarstig Anders , Andersson Charlotte , Verweij Niek , Holmes Michael V. , Ärnlöv Johan , Svensson Per , Hemingway Harry , Sallah Neneh , Almgren Peter , Aragam Krishna G. , Asselin Geraldine , Backman Joshua D. , Biggs Mary L. , Bloom Heather L. , Boersma Eric , Brandimarto Jeffrey , Brown Michael R. , Brunner‐La Rocca Hans‐Peter , Carey David J. , Chaffin Mark D. , Chasman Daniel I. , Chazara Olympe , Chen Xing , Chen Xu , Chung Jonathan H. , Chutkow William , Cleland John G.F. , Cook James P. , de Denus Simon , Dehghan Abbas , Delgado Graciela E. , Denaxas Spiros , Doney Alexander S. , Dörr Marcus , Dudley Samuel C. , Engström Gunnar , Esko Tõnu , Fatemifar Ghazaleh , Felix Stephan B. , Finan Chris , Ford Ian , Fougerousse Francoise , Fouodjio René , Ghanbari Mohsen , Ghasemi Sahar , Giedraitis Vilmantas , Giulianini Franco , Gottdiener John S. , Gross Stefan , Guðbjartsson Daníel F. , Gui Hongsheng , Gutmann Rebecca , Haggerty Christopher M. , van der Harst Pim , Hedman Åsa K. , Helgadottir Anna , Hillege Hans , Hyde Craig L. , Jacob Jaison , Jukema J. Wouter , Kamanu Frederick , Kardys Isabella , Kavousi Maryam , Khaw Kay‐Tee , Kleber Marcus E. , Køber Lars , Koekemoer Andrea , Kraus Bill , Kuchenbaecker Karoline , Langenberg Claudia , Lind Lars , Lindgren Cecilia M. , London Barry , Lotta Luca A. , Lovering Ruth C. , Luan Jian'an , Magnusson Patrik , Mahajan Anubha , Mann Douglas , Margulies Kenneth B. , Marston Nicholas A. , März Winfried , McMurray John J.V. , Melander Olle , Melloni Giorgio , Mordi Ify R. , Morley Michael P. , Morris Andrew D. , Morris Andrew P. , Morrison Alanna C. , Nagle Michael W. , Nelson Christopher P. , Newton‐Cheh Christopher , Niessner Alexander , Niiranen Teemu , Nowak Christoph , O'Donoghue Michelle L. , Owens Anjali T. , Palmer Colin N.A. , Paré Guillaume , Perola Markus , Perreault Louis‐Philippe Lemieux , Portilla‐Fernandez Eliana , Psaty Bruce M. , Rice Kenneth M. , Ridker Paul M. , Romaine Simon P.R. , Roselli Carolina , Rotter Jerome I. , Ruff Christian T. , Sabatine Marc S. , Salo Perttu , Salomaa Veikko , van Setten Jessica , Shalaby Alaa A. , Smelser Diane T. , Smith Nicholas L. , Stefansson Kari , Stender Steen , Stott David J. , Sveinbjörnsson Garðar , Tammesoo Mari‐Liis , Tardif Jean‐Claude , Taylor Kent D. , Teder‐Laving Maris , Teumer Alexander , Thorgeirsson Guðmundur , Thorsteinsdottir Unnur , Torp‐Pedersen Christian , Trompet Stella , Tuckwell Danny , Tyl Benoit , Uitterlinden Andre G. , Vaura Felix , Veluchamy Abirami , Visscher Peter M. , Völker Uwe , Voors Adriaan A. , Wang Xiaosong , Wareham Nicholas J. , Weeke Peter E. , Weiss Raul , White Harvey D. , Wiggins Kerri L. , Xing Heming , Yang Jian , Yang Yifan , Yerges‐Armstrong Laura M. , Yu Bing , Zannad Faiez , Zhao Faye ,   Regeneron Genetics Center, Wilk Jemma B. , Holm Hilma , Sattar Naveed , Lubitz Steven A. , Lanfear David E. , Shah Svati , Dunn Michael E. , Wells Quinn S. , Asselbergs Folkert W. , Hingorani Aroon D. , Dubé Marie‐Pierre , Samani Nilesh J. , Lang Chim C. , Cappola Thomas P. , Ellinor Patrick T. , Vasan Ramachandran S. , Smith J. Gustav 
Published: September 2021

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.