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

Regeneron Genetics Ctr, R. Thomas Lumbers, Sonia Shah, Honghuang Lin, Tomasz Czuba, Albert Henry, Daniel Swerdlow, Anders Malarstig, Charlotte Andersson, Niek Verweij, Michael Holmes, Johan Arnlov, 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 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 Doerr, Samuel C. Dudley, Gunnar Engstrom, Tonu Esko, Ghazaleh Fatemifar, Pim van der Harst, Hans Hillege, Carolina Roselli, Peter M. Visscher, Adriaan A. Voors, Folkert W. Asselbergs

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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 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 languageEnglish
Article number8
Pages (from-to)5531–5541
Number of pages11
JournalESC Heart Failure
Early online date3-Sep-2021
DOIs
Publication statusPublished - 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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