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


ABSTRACT: 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.

SUBMITTER: Patel RS 

PROVIDER: S-EPMC3459582 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Patel Riyaz S RS   Sun Yan V YV   Hartiala Jaana J   Veledar Emir E   Su Shaoyong S   Sher Salman S   Liu Ying X YX   Rahman Ayaz A   Patel Ronak R   Rab S Tanveer ST   Vaccarino Viola V   Zafari A Maziar AM   Samady Habib H   Tang W H Wilson WH   Allayee Hooman H   Hazen Stanley L SL   Quyyumi Arshed A AA  

Circulation. Cardiovascular genetics 20120705 4


<h4>Background</h4>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.<h4>Methods and results</h4>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 follow  ...[more]

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