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Circ Cardiovasc Genet. 2012 Aug 1;5(4):441-9. doi: 10.1161/CIRCGENETICS.111.960229. Epub 2012 Jul 5.

Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.

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Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.



Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established.


In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls ≥70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (≥70 years of age) with no history of MI (P<0.001). This association was successfully replicated in a second cohort, yielding a pooled P value of <0.001. The GRS modestly improved the area-under-the-curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with s\ angiographic CAD were examined (pooled P=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort.


A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction.

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