Predictive Accuracy of a Polygenic Risk Score Compared With a Clinical Risk Score for Incident Coronary Heart Disease
Authors' conclusion
In this analysis of 2 cohorts of US adults, the polygenic risk score was associated with incident coronary heart disease events but did not significantly improve discrimination, calibration, or risk reclassification compared with conventional predictors.
Study context
- Population
- US adults of white European ancestry aged 45–79 years in Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA), 1996–2015
- Participants
- 4,847 vs 2,390
- Exposure
- PCE plus polygenic risk score vs PCE alone
- ARICn = 4,847
- MESAn = 2,390
- Outcome
- Prediction of first coronary heart disease (CHD) events (MI, fatal coronary events, silent infarctions, revascularization, resuscitated cardiac arrest): discrimination, calibration, NRI
- Follow-up
- 10-year
Methodological details2 cohorts (ARIC, MESA)
- 2 cohorts (ARIC, MESA)
Main finding
As reported in the abstract
Prediction of 10-year CHD: PCE + polygenic risk score vs PCE
- ARIC
- change in C statistic −0.001 (95% CI −0.009 to 0.006)
- MESA
- change in C statistic 0.021 (95% CI −0.0004 to 0.043)
- ARIC · at 10-year risk threshold of 7.5%
- Net reclassification improvement (NRI) 0.018 (95% CI −0.012 to 0.036)
- MESA · at 10-year risk threshold of 7.5%
- NRI 0.001 (95% CI −0.038 to 0.076)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Association of polygenic risk score with 10-year CHD incidence (HR per SD increment)ARIC · per SD increment | 1.24 (1.15–1.34) | |
| Association of polygenic risk score with 10-year CHD incidence (HR per SD increment)MESA · per SD increment | 1.38 (1.21–1.58) | |
| 0.512Hazard ratio (log scale) |
Incident CHD events · median follow-up 15.5 years (ARIC), 14.2 years (MESA)
Original publication
Predictive Accuracy of a Polygenic Risk Score Compared With a Clinical Risk Score for Incident Coronary Heart Disease. JAMA. Published 18 February 2020. doi:10.
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