Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Résumé
Introduction
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.
Méthodes
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.
Résultats
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.
Conclusions
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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet. 2004; 364: 937-952
- Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE).Lancet. 2000; 356: 279-284
- A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.Nat Genet. 2011; 43: 339-344
- Large-scale association analysis identifies new risk loci for coronary artery disease.Nat Genet. 2013; 45: 25-33
- Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.Nat Genet. 2011; 43: 333-338
- A common allele on chromosome 9 associated with coronary heart disease.Science. 2007; 316: 1488-1491
- A common variant on chromosome 9p21 affects the risk of myocardial infarction.Science. 2007; 316: 1491-1493
- Genomewide association analysis of coronary artery disease.N Engl J Med. 2007; 357: 443-453
- Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.Nat Genet. 2009; 41: 334-341
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.Nature. 2007; 447: 661-678
- A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses.Lancet. 2010; 376: 1393-1400
- Literature-based genetic risk scores for coronary heart disease: the Cardiovascular Registry Maastricht (CAREMA) prospective cohort study.Circ Cardiovasc Genet. 2012; 5: 202-209
- A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.Circ Cardiovasc Genet. 2012; 5: 113-121
- Multilocus genetic risk scores for coronary heart disease prediction.Arterioscler Thromb Vasc Biol. 2013; 33: 2267-2272
- Accounting for ancestry: population substructure and genome-wide association studies.Hum Mol Genet. 2008; 17: R143-R150
- Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: The EpiDREAM genetic study.Diabetes Care. 2013; 36: 2836-2842
- Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study.Lancet. 2004; 364: 953-962
- Higgens J.P.T. Green S. Cochrane Handbook for Systematic Reviews of Interventions, version 5.0.0. The Cochrane Collaboration, 2008
- Variance calculations and confidence intervals for estimates of the attributable risk based on logistic models.Biometrics. 1990; 46: 991-1003
- Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.Stat Med. 2008; 27: 157-172
- Accounting for linkage disequilibrium in association analysis of diverse populations.Genet Epidemiol. 2014; 38: 265-273
- Genome-wide association studies: implications for multiethnic samples.Hum Mol Genet. 2008; 17: R151-R155
- A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies.Atherosclerosis. 2012; 223: 421-426
- Genetic risk score and risk of myocardial infarction in Hispanics.Circulation. 2011; 123: 374-380
- Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.PLoS Genet. 2012; 8: e1002554
- Loss-of-function mutations in APOC3, triglycerides, and coronary disease.N Engl J Med. 2014; 371: 22-31
- Inactivating mutations in NPC1L1 and protection from coronary heart disease.N Engl J Med. 2014; 371: 2072-2082
Article info
Publication history
Published online: June 02, 2016
Accepted:
May 25,
2016
Received:
March 13,
2016
Footnotes
See editorial by McPherson and Hegele, pages 1372–1374 of this issue.
See page 1445 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
