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Title | Genome-Wide Polygenic Score, Clinical Risk Factors, and Long-Term Trajectories of Coronary Artery Disease. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Hindy, G, Aragam, KG, Ng, K, Chaffin, M, Lotta, LA, Baras, A, Drake, I, Orho-Melander, M, Melander, O, Kathiresan, S, Khera, AV |
Corporate Authors | Regeneron Genetics Center |
Journal | Arterioscler Thromb Vasc Biol |
Volume | 40 |
Issue | 11 |
Pagination | 2738-2746 |
Date Published | 2020 11 |
ISSN | 1524-4636 |
Keywords | Adult, Aged, Coronary Artery Disease, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Disease Risk Factors, Heredity, Humans, Incidence, Male, Middle Aged, Multifactorial Inheritance, Phenotype, Prognosis, Risk Assessment, Sweden, Time Factors, United Kingdom |
Abstract | OBJECTIVE: To determine the relationship of a genome-wide polygenic score for coronary artery disease (GPS) with lifetime trajectories of CAD risk, directly compare its predictive capacity to traditional risk factors, and assess its interplay with the Pooled Cohort Equations (PCE) clinical risk estimator. Approach and Results: We studied GPS in 28 556 middle-aged participants of the Malmö Diet and Cancer Study, of whom 4122 (14.4%) developed CAD over a median follow-up of 21.3 years. A pronounced gradient in lifetime risk of CAD was observed-16% for those in the lowest GPS decile to 48% in the highest. We evaluated the discriminative capacity of the GPS-as assessed by change in the C-statistic from a baseline model including age and sex-among 5685 individuals with PCE risk estimates available. The increment for the GPS (+0.045, CONCLUSIONS: GPS-a risk estimator available from birth-stratifies individuals into varying trajectories of clinical risk for CAD. Implementation of GPS may enable identification of high-risk individuals early in life, decades in advance of manifest risk factors or disease. |
DOI | 10.1161/ATVBAHA.120.314856 |
Alternate Journal | Arterioscler Thromb Vasc Biol |
PubMed ID | 32957805 |
PubMed Central ID | PMC7577949 |
Grant List | K08 HG010155 / HG / NHGRI NIH HHS / United States MC_PC_17228 / MR / Medical Research Council / United Kingdom MC_QA137853 / MR / Medical Research Council / United Kingdom UM1 HG008895 / HG / NHGRI NIH HHS / United States |