Development and Evaluation of a Comprehensive Prediction Model for Incident Coronary Heart Disease Using Genetic, Social, and Lifestyle-Psychological Factors: A Prospective Analysis of the UK Biobank.

Abstract

Clinical risk calculators for coronary heart disease (CHD) do not include genetic, social, and lifestyle-psychological risk factors. To improve CHD risk prediction by developing and evaluating a prediction model that incorporated a polygenic risk score (PRS) and a polysocial score (PSS), the latter including social determinants of health and lifestyle-psychological factors. Cohort study. United Kingdom. UK Biobank participants recruited between 2006 and 2010. Incident CHD (myocardial infarction and/or coronary revascularization); 10-year clinical risk based on pooled cohort equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and QRISK3; PRS (Polygenic Score Catalog identification: PGS000018) for CHD (PRSCHD); and PSSCHD from 100 related covariates. Machine-learning and time-to-event analyses and model performance indices. In 388 224 participants (age, 55.5 [SD, 8.1] years; 42.5% men; 94.9% White), the hazard ratio for 1 SD increase in PSSCHD for incident CHD was 1.43 (95% CI, 1.38 to 1.49; P < 0.001) and for 1 SD increase in PRSCHD was 1.59 (CI, 1.53 to 1.66, P < 0.001). Non-White persons had higher PSSCHD than White persons. The effects of PSSCHD and PRSCHD on CHD were independent and additive. At a 10-year CHD risk threshold of 7.5%, adding PSSCHD and PRSCHD to PCE reclassified 12% of participants, with 1.86 times higher CHD risk in the up- versus down-reclassified persons and showed superior performance compared with PCE as reflected by improved net benefit while maintaining good calibration relative to the clinical risk calculators. Similar results were seen when incorporating PSSCHD and PRSCHD into PREVENT and QRISK3. A predominantly White cohort; possible healthy participant effect and ecological fallacy. A PSSCHD was associated with incident CHD and its joint modeling with PRSCHD improved the performance of clinical risk calculators. National Human Genome Research Institute.