All participating cohorts either measured RR-intervals from the standard 12-lead electrocardiogram (ECG) or used HR measurements (in beats per minute) from peripheral pulse measurements (Supplementary Material, Table S14), which were converted to the RR-interval scale (in milliseconds) using the inverse relationship formula: RR (ms) = 60 000/HR (BPM). The discovery analysis was undertaken using the RR-interval phenotype. The exclusion criteria included: extreme RR-intervals (< 600 or > 1500 ms), atrial fibrillation on the ECG, a history of myocardial infarction or heart failure, use of non-dihydropyridine calcium-antagonists [Anatomic Therapeutic Chemical (ATC) code C08D], digoxin (ATC code C01AA5), second or third degree atrioventricular block and a pacemaker signal on the ECG. Local ethics committees approved the contributing studies from the CHARGE consortium, and all individuals provided their consent in writing. The UK Biobank study has approval from the North West Multi-centre Research Ethics Committee and has Research Tissue Bank approval.
