Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men.
Circ Genom Precis Med
; 14(6): e003452, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34670400
ABSTRACT
BACKGROUND:
Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.METHODS:
A PRSCAD including the weighted effects of >1.14 million single nucleotide polymorphisms associated with CAD was calculated in UK Biobank (n=408 422), using LDpred. Cox regressions were performed, stratified by age quartiles and sex, for incident myocardial infarction (MI) and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).RESULTS:
From 7746 incident MI cases and 393 725 controls, hazard ratio for MI reached 1.53 (95% CI, 1.49-1.56; P=2.69×10-296) per SD increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction P=0.002), particularly in those aged between 40 and 51 years (hazard ratio, 2.00 [95% CI, 1.86-2.16], P=1.93×10-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02, 0.199 [95% CI, 0.157-0.248] and NRI>0, 0.602 [95% CI, 0.525-0.683]). From 23 982 deaths, hazard ratio for mortality was 1.08 (95% CI, 1.06-1.09; P=5.46×10-30) per SD increase of PRSCAD, with a stronger association in men (interaction P=1.60×10-6).CONCLUSIONS:
Our PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40 and 51 years. PRS could optimize the identification and management of individuals at risk for CAD.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
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Infarto del Miocardio
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2021
Tipo del documento:
Article