title: Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations.
abstract: Myocardial infarction (MI) risk varies by ethnicity, although the influence of genetic factors remains unclear. Using a genetic risk score (GRS), we examined the association between 25 coronary artery disease (CAD)-related single nucleotide polymorphisms and MI across 6 ethnic groups.
  
  
  
  We studied 8556 participants in the INTERHEART case-control study from 6 ethnic groups: Europeans, South Asians, Southeast Asians, Arabs, Latin Americans, and Africans. Associations between the GRS and MI were tested in each group by logistic regression and overall by meta-analysis.
  
  
  
  Overall, the GRS increased the odds of MI by 1.07 (95% confidence interval [CI], 1.04-1.09) per risk allele in the unadjusted model, with little change (odds ratio, 1.06; 95% CI, 1.04-1.09) after adjusting for demographic and modifiable factors. In Europeans, South Asians, Southeast Asians, and Arabs, the GRS was significantly associated with MI, with minimal heterogeneity observed. In these groups, a score > 23 risk alleles (highest 4 quintiles) was associated with only a 5% difference in population attributable risk (PAR) (36% to 41%) for MI. The GRS was not significant in Latin Americans or Africans. In the overall cohort, modest changes, beyond clinical factors, in PAR (88% to 91%), concordance statistic (0.73 to 0.74), and continuous net reclassification improvement (12%) were observed with the GRS.
  
  
  
  A CAD GRS is associated with MI across a multiethnic cohort, with significant and consistent effects across 4 distinct ethnicities. However, it only modestly improves MI risk prediction beyond clinical factors.
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address: philip.joseph@phri.ca.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Joseph
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Senay
authors.initials: S
authors.lastname: Asma
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
mesh_terms: D016022:Case-Control Studies; D015987:Effect Modifier, Epidemiologic; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012107:Research Design; D012307:Risk Factors
chemical_list: D005819:Genetic Markers