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

Riyaz S. Patel, Yan V. Sun, Jaana Hartiala, Emir Veledar, Shaoyong Su, Salman Sher, Ying X. Liu, Ayaz Rahman, Ronak Patel, S. Tanveer Rab, Viola Vaccarino, A. Maziar Zafari, Habib Samady, W. H. Wilson Tang, Hooman Allayee, Stanley L. Hazen, Arshed A. Quyyumi

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: 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. Methods and Results: 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 stable 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
JournalCirculation: Cardiovascular Genetics
Volume5
Issue number4
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cardiovascular disease risk factors
  • Coronary artery disease
  • Genetic risk score
  • Myocardial infarction

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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