Genetic risk score and risk of myocardial infarction in Hispanics.
BACKGROUND
Genome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics.


RESULTS
Cases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval [CI], 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70).


CONCLUSIONS
These results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA. nhlqi@channing.harvard.edu
Lu
L
Qi
Jiantao
J
Ma
Qibin
Q
Qi
Jaana
J
Hartiala
Hooman
H
Allayee
Hannia
H
Campos
D000368:Aged; D015820:Cadherins / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics; D003364:Costa Rica / Q000453:epidemiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
C498477:CELSR2 protein, human; C515255:CXCL12 protein, human; D015820:Cadherins; D054377:Chemokine CXCL12; D019941:Cyclin-Dependent Kinase Inhibitor p16
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