MSGene: a multistate model using genetic risk and the electronic health record applied to lifetime risk of coronary artery disease.

Autor: Urbut SM; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA., Yeung MW; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Khurshid S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Demoulas Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, MA, USA., Cho SMJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea., Schuermans A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Faculty of Medicine, KU Leuven, Leuven, Belgium., German J; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.; Eric and Wendy Schmidt Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Taraszka K; Division of Population Sciences, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA, USA., Paruchuri K; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA., Fahed AC; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Ellinor PT; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Demoulas Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, MA, USA., Trinquart L; Institute for Clinical Research and Health Policy Studies (ICRHPS), Tufts Medical Center, Boston, MA, USA.; Tufts Clinical and Translational Science Institute (CTSI), Tufts University, Boston, MA, USA., Parmigiani G; Department of Data Science, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Gusev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Population Sciences, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA, USA., Natarajan P; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. pnatarajan@mgh.harvard.edu.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. pnatarajan@mgh.harvard.edu.; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. pnatarajan@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 07; Vol. 15 (1), pp. 4884. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1038/s41467-024-49296-9
Abstrakt: Coronary artery disease (CAD) is the leading cause of death among adults worldwide. Accurate risk stratification can support optimal lifetime prevention. Current methods lack the ability to incorporate new information throughout the life course or to combine innate genetic risk factors with acquired lifetime risk. We designed a general multistate model (MSGene) to estimate age-specific transitions across 10 cardiometabolic states, dependent on clinical covariates and a CAD polygenic risk score. This model is designed to handle longitudinal data over the lifetime to address this unmet need and support clinical decision-making. We analyze longitudinal data from 480,638 UK Biobank participants and compared predicted lifetime risk with the 30-year Framingham risk score. MSGene improves discrimination (C-index 0.71 vs 0.66), age of high-risk detection (C-index 0.73 vs 0.52), and overall prediction (RMSE 1.1% vs 10.9%), in held-out data. We also use MSGene to refine estimates of lifetime absolute risk reduction from statin initiation. Our findings underscore our multistate model's potential public health value for accurate lifetime CAD risk estimation using clinical factors and increasingly available genetics toward earlier more effective prevention.
(© 2024. The Author(s).)
Databáze: MEDLINE
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