The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. The consortium currently includes 51 studies fro Show more
The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. 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 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. Show less
Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been validated Show more
Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been validated by multiple groups. We performed a case-control study to further investigate the potential impact of 14 previously reported candidate genes on the risk of HF and specific HF sub-types. We also performed an exploratory genome-wide study. We included 799 patients with HF and 1529 controls. After adjusting for age, sex, and genetic ancestry, we found that the C allele of rs2234962 in BAG3 was associated with a decreased risk of idiopathic dilated cardiomyopathy (odds ratio 0.42, 95% confidence interval 0.25-0.68, P = 0.0005), consistent with a previous report. No association for the other primary variants or exploratory genome-wide study was found. Our findings provide independent replication for the association between a common coding variant (rs2234962) in BAG3 and the risk of idiopathic dilated cardiomyopathy. Show less