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Olle Melander

Principal investigator

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Genome-Wide Polygenic Score, Clinical Risk Factors, and Long-Term Trajectories of Coronary Artery Disease

Author

  • George Hindy
  • Krishna G. Aragam
  • Kenney Ng
  • Mark Chaffin
  • Luca A. Lotta
  • Aris Baras
  • Isabel Drake
  • Marju Orho-Melander
  • Olle Melander
  • Sekar Kathiresan
  • Amit V. Khera

Summary, in English

OBJECTIVE: To determine the relationship of a genome-wide polygenic score for coronary artery disease (GPSCAD) 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 GPSCAD 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 GPSCAD decile to 48% in the highest. We evaluated the discriminative capacity of the GPSCAD-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 GPSCAD (+0.045, P<0.001) was higher than for any of 11 traditional risk factors (range +0.007 to +0.032). Minimal correlation was observed between GPSCAD and 10-year risk defined by the PCE (r=0.03), and addition of GPSCAD improved the C-statistic of the PCE model by 0.026. A significant gradient in lifetime risk was observed for the GPSCAD, even among individuals within a given PCE clinical risk stratum. We replicated key findings-noting strikingly consistent results-in 325 003 participants of the UK Biobank. CONCLUSIONS: GPSCAD-a risk estimator available from birth-stratifies individuals into varying trajectories of clinical risk for CAD. Implementation of GPSCAD may enable identification of high-risk individuals early in life, decades in advance of manifest risk factors or disease.

Department/s

  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Hypertension

Publishing year

2020

Language

English

Pages

2738-2746

Publication/Series

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

40

Issue

11

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • coronary artery disease
  • disease
  • genome
  • risk factors
  • statistics

Status

Published

Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1524-4636