Fig. 2

The role of DNAm AgeAccelPheno in mediating the relationship between any CV risk factor and the ECG-based outcomes. We defined the presence of any CV risk factor as participants having at least one out of: diabetes, high cholesterol, hypertension, CVD, or a BMI > 30. On average, DNAm AgeAccelPheno mediates 10–20% of the relationships between any CV risk factor and the ECG-based cardiac ages (panel A) and disease scores (panel B). Either  a more positive ECG-based cardiac age or  a more negative ECG-based disease score represent a worse phenotype. Abbreviations: aECG = advanced electrocardiography; ACME = average causal mediation effect; ADE = average direct effect; DNN = deep neural network; LVER = left ventricular electrical remodelling; LVSD = left ventricular systolic dysfunction. Other abbreviations as in Fig. 1