title: Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography.
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.
  
  
  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 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.
  
  
  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.
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Riyaz S
authors: RS
authors: Patel
authors: Yan V
authors: YV
authors: Sun
authors: Jaana
authors: J
authors: Hartiala
authors: Emir
authors: E
authors: Veledar
authors: Shaoyong
authors: S
authors: Su
authors: Salman
authors: S
authors: Sher
authors: Ying X
authors: YX
authors: Liu
authors: Ayaz
authors: A
authors: Rahman
authors: Ronak
authors: R
authors: Patel
authors: S Tanveer
authors: ST
authors: Rab
authors: Viola
authors: V
authors: Vaccarino
authors: A Maziar
authors: AM
authors: Zafari
authors: Habib
authors: H
authors: Samady
authors: W H Wilson
authors: WH
authors: Tang
authors: Hooman
authors: H
authors: Allayee
authors: Stanley L
authors: SL
authors: Hazen
authors: Arshed A
authors: AA
authors: Quyyumi
mesh_terms: D000368:Aged; D015331:Cohort Studies; D017023:Coronary Angiography; D003710:Demography; D016002:Discriminant Analysis; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005845:Georgia / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors