Back to Search
Start Over
Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses
- Source :
- PLoS Medicine, Vol 18, Iss 1, p e1003498 (2021), PLoS Medicine
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- Background Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. Methods and findings Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to<br />Luanluan Sun and colleagues investigate whether adding polygenic risk scores to conventional risk factors of cardiovascular disease helps predict disease risk.<br />Author summary Why was this study done? Application of polygenic risk scores (PRSs) has opened opportunities to enhance risk stratification and prevention for common diseases. The clinical utility of PRSs in cardiovascular disease (CVD) risk prediction is, however, uncertain. Previous analyses have generally focused only on coronary heart disease (CHD) rather than the composite outcome of CHD and stroke, and have often lacked modelling of clinical implications of initiating guideline-recommended interventions (e.g., statin therapy). What did the researchers do and find? We quantified the incremental predictive gain with PRSs on top of conventional risk factors using data on 306,654 individuals from UK Biobank. We modelled the population health implications of initiating statin therapy as recommended by current guidelines using data from 2.1 million individuals from the Clinical Practice Research Datalink. Addition of information on PRSs to a conventional risk prediction model increased the C-index (a measure of risk discrimination) and improved risk classification of cases and non-cases. We estimated that targeted assessment of PRSs among people at intermediate (i.e., 5% to
- Subjects :
- Male
Epidemiology
030204 cardiovascular system & hematology
Cardiovascular Medicine
Biochemistry
Vascular Medicine
Cohort Studies
Welsh
0302 clinical medicine
Medical Conditions
Endocrinology
Agency (sociology)
Coronary Heart Disease
030212 general & internal medicine
Incidence
General Medicine
Middle Aged
Medical research
C-Reactive Proteins
Lipids
Social research
Stroke
Cholesterol
Neurology
Cardiovascular Diseases
language
Medicine
Female
Cohort study
Research Article
Adult
medicine.medical_specialty
Endocrine Disorders
Cerebrovascular Diseases
Cardiology
Library science
Risk Assessment
03 medical and health sciences
Political science
medicine
Diabetes Mellitus
Humans
Ischemic Stroke
Aged
Medicine and health sciences
Government
Biology and life sciences
Public health
Proteins
Cardiovascular Disease Risk
language.human_language
United Kingdom
Heart Disease Risk Factors
Medical Risk Factors
Metabolic Disorders
Polygenic risk score
Biomarkers
Subjects
Details
- ISSN :
- 15491277
- Database :
- OpenAIRE
- Journal :
- PLoS Medicine, Vol 18, Iss 1, p e1003498 (2021), PLoS Medicine
- Accession number :
- edsair.doi.dedup.....90e1e1fb98f4e5c5ac71dafb8f858759