Canadian Journal of Cardiology
Clinical Research| Volume 32, ISSUE 12, P1440-1446, December 2016

Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations



      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.



      L’infarctus du myocarde (IM) varie selon l’origine ethnique, bien que l’influence des facteurs génétiques demeure obscure. À l’aide du score de risque génétique (SRG), nous avons examiné l’association entre 25 polymorphismes de nucléotide simple liés à la coronaropathie (CP) et l’IM de 6 groupes ethniques.


      Nous avons étudié 8556 participants de l’étude cas-témoins INTERHEART issus de 6 groupes ethniques : les Européens, les Asiatiques du Sud, les Asiatiques du Sud-Est, les Arabes, les Latino-Américains et les Africains. Nous avons vérifié les associations entre le SRG et l’IM de chaque groupe par régression logistique et de l’ensemble par méta-analyse.


      Dans l’ensemble, le SRG augmentait la probabilité de l’IM de 1,07 (intervalle de confiance [IC] à 95 %, 1,04-1,09) par allèle de risque dans le modèle non ajusté, et montrait peu de changement (ratio d’incidence approché, 1,06; IC à 95 %, 1,04-1,09) après l’ajustement des facteurs démographiques et modifiables. Chez les Européens, les Asiatiques du Sud, les Asiatiques du Sud-Est et les Arabes, le SRG était significativement associé à l’IM et montrait une hétérogénéité minimale. Dans ces groupes, un score > 23 allèles de risque (4 quintiles les plus élevés) était associé à une différence de seulement 5 % dans le risque attribuable dans la population (RAP) (36 % à 41 %) pour l'IM. Le SRG n’était pas significatif chez les Latino-Américains ou les Africains. Dans l’ensemble de la cohorte, des changements modestes, au-delà des facteurs cliniques, dans le RAP (88 % à 91 %), la statistique de concordance (0,73 à 0,74) et l’amélioration nette continue de la reclassification (12 %) étaient observés avec le SRG.


      Un SRG de CP est associé à l’IM dans toute la cohorte multiethnique et montre particulièrement des effets significatifs et cohérents dans 4 origines ethniques. Cependant, il n’améliore que modestement la prédiction du risque d’IM au-delà des facteurs cliniques.
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