Phenotyping

Disease phenotypes in UK Biobank were defined using a combination of self-reported questionnaire data (confirmed by a trained healthcare professional) and linked hospital-admission and death registry data. Detailed definitions for all disease phenotypes are provided in Supplemental Table S1.

We defined “all-cause” HF as the presence of self-reported “HF/pulmonary edema” or “cardiomyopathy” at any visit; or an International Classification of Diseases (ICD)-10 or ICD-9 billing code indicative of heart/ventricular failure or a cardiomyopathy of any cause. Of note, individuals with a diagnosis of hypertrophic cardiomyopathy – as ascertained by self-report or by pertinent ICD-10 codes – were excluded from the HF and NICM phenotypes even if they met the above criteria due to the substantial Mendelian inheritance pattern of hypertrophic cardiomyopathy.

Among all-cause HF patients, we defined “nonischemic cardiomyopathy” (NICM) on the basis of left ventricular dysfunction and absence of coronary artery disease (CAD). A priori, individuals were considered to have “left ventricular dysfunction” if they carried ICD-10 diagnoses of “dilated cardiomyopathy” or “left ventricular failure,” or an ICD-9 diagnosis of “left heart failure.” Indicators for CAD included myocardial infarction or coronary revascularization, as described previously.¹⁰ Myocardial infarction was defined as a self-report of “heart attack” or an ICD-10 code of acute myocardial infarction. Coronary revascularization was defined as the presence of an operative or procedure code for coronary artery bypass surgery or coronary angioplasty (Supplemental Table S1).