Abstract 17892: A Genetic Risk Score of Novel Variants is Predictive of Myocardial Infarction Risk
Background: Genome-Wide Association Studies have identified multiple myocardial infarction (MI) risk variants, with one study demonstrating cumulative MI risk with an increasing number of risk alleles in Caucasians. Independent replication validating such a score is lacking. We hypothesized that a genetic MI risk score would be predictive of a) prevalent MI risk and b) of adverse outcomes in a high risk population.
Methods: All subjects were recruited from the Emory Cardiology Biobank, a registry of patients undergoing cardiac catheterization. We first identified those with a history of MI at any age prior to 70yrs and controls as those without MI aged 70yrs or above at enrollment to assess MI risk and mitigate case misclassification bias. Follow up was performed for a median of 2.6 years with the primary endpoint of cardiovascular death/MI. We Genotyped 11 validated MI risk variants (at loci 1p13, 1p32, 1q41, 2q33, 3q22, 6p24, 9p21, 10q11, 12q24, 19p13, 21q22) on all subjects. Genetic risk scores were calculated using (1) risk allele counting and (2) weighting by published effect sizes.
Results: We examined a total of 2457 Caucasian subjects (mean age 62.8 (11.6), male 65.6%). As continuous traits, both the allelic and weighted genetic risk scores were associated with a risk of MI (both p <0.0001; 889 cases & 449 controls) which persisted after adjustment for age, gender, risk factors and medications (p<0.001, p=0.008). When grouped as quintiles both scores were again associated with increasing MI risk (Figure 1). During follow-up of all 2457 subjects, there were 168 adverse events, but there was no association between the risk scores and events during this follow-up period.
Conclusion: A genetic risk score based on currently discovered MI risk variants is predictive of risk of MI before the age of 70, but not short term risk of adverse events in a high risk population. Such scores may be of most value in predicting lifetime risk and to aid behavior modification in early life.
- © 2010 by American Heart Association, Inc.