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.

Arrhythmic Sudden Cardiac Death in Heart Failure With Preserved Ejection Fraction: Mechanisms, Genetics, and Future Directions

“…Adapted with permission from: The genomics of heart failure: design and rationale of the HERMES consortium. 67 J o u r n a l P r e -p r o o f…”

“…This analysis was the first published from the He art Failure M olecular E pidemiology for Therapeutic Target s (HERMES) consortium and was designed to address undifferentiated HF syndrome to maximal statistical power and discover genetic contributions to common pathophysiological mechanisms. 67 One limitation with this trial, however, is that all participants are of European ancestry, limiting the generalizability to other populations and clinical practice.

Figure 2 Common genetic variants found in genome-wide association studies of heart failure.

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“…Reproduced from Lumbers et al. 67 under Creative Commons Attribution 4.0 International (CC BY 4.0) license. …”

“…Common genetic variants found in genome-wide association studies of heart failure.Most studies to date have failed to differentiate patients by ejection fraction and so phenotypespecific data on HFpEF and HFrEF is scarce. Adapted with permission from: The genomics of heart failure: design and rationale of the HERMES consortium 67.…”

Biomarkers of heart failure: advances in omics studies

“…Rapid advances in genetic and genomic technologies, ranging from targeted multi-gene genetic testing panels to whole-exome and whole-genome sequencing, have transformed our understanding of the genetic and genomic contribution to HF beyond large family studies and segregation analyses. 10,11 HF is hereditary, with a heritability of about 18%. A history of HF in parents can increase the risk of the disease in their offspring.…”