Predictive Accuracy of a Polygenic Risk Score-Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease.
JAMA
; 323(7): 636-645, 2020 02 18.
Article
en En
| MEDLINE
| ID: mdl-32068818
ABSTRACT
Importance The incremental value of polygenic risk scores in addition to well-established risk prediction models for coronary artery disease (CAD) is uncertain. Objective:
To examine whether a polygenic risk score for CAD improves risk prediction beyond pooled cohort equations. Design, Setting, andParticipants:
Observational study of UK Biobank participants enrolled from 2006 to 2010. A case-control sample of 15â¯947 prevalent CAD cases and equal number of age and sex frequency-matched controls was used to optimize the predictive performance of a polygenic risk score for CAD based on summary statistics from published genome-wide association studies. A separate cohort of 352â¯660 individuals (with follow-up to 2017) was used to evaluate the predictive accuracy of the polygenic risk score, pooled cohort equations, and both combined for incident CAD. Exposures Polygenic risk score for CAD, pooled cohort equations, and both combined. Main Outcomes andMeasures:
CAD (myocardial infarction and its related sequelae). Discrimination, calibration, and reclassification using a risk threshold of 7.5% were assessed.Results:
In the cohort of 352â¯660 participants (mean age, 55.9 years; 205â¯297 women [58.2%]) used to evaluate the predictive accuracy of the examined models, there were 6272 incident CAD events over a median of 8 years of follow-up. CAD discrimination for polygenic risk score, pooled cohort equations, and both combined resulted in C statistics of 0.61 (95% CI, 0.60 to 0.62), 0.76 (95% CI, 0.75 to 0.77), and 0.78 (95% CI, 0.77 to 0.79), respectively. The change in C statistic between the latter 2 models was 0.02 (95% CI, 0.01 to 0.03). Calibration of the models showed overestimation of risk by pooled cohort equations, which was corrected after recalibration. Using a risk threshold of 7.5%, addition of the polygenic risk score to pooled cohort equations resulted in a net reclassification improvement of 4.4% (95% CI, 3.5% to 5.3%) for cases and -0.4% (95% CI, -0.5% to -0.4%) for noncases (overall net reclassification improvement, 4.0% [95% CI, 3.1% to 4.9%]). Conclusions and Relevance The addition of a polygenic risk score for CAD to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals. The use of genetic information over the pooled cohort equations model warrants further investigation before clinical implementation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
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Medición de Riesgo
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Predisposición Genética a la Enfermedad
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Herencia Multifactorial
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
JAMA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido