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Published on: April 1, 2019
Are myocardial infarction--associated single-nucleotide polymorphisms associated with ischemic stroke?
Yu-Ching Cheng1, Christopher D Anderson, Silvia Bione
1Department of Medicine, University of Maryland School of Medicine, 660 W Redwood St, Howard Hall, Room 492, Baltimore, MD 21201, USA.
Insights
Genetic variants linked to heart attacks (myocardial infarction) and coronary artery disease do not appear to significantly increase ischemic stroke risk. Further research may explore associations with specific stroke subtypes.
Area of Science:
- Genetics
- Cardiovascular Disease
- Neurology
Background:
- Ischemic stroke (IS) and coronary artery disease (CAD) share common risk factors.
- Genetic predisposition may play a role in both conditions.
Purpose of the Study:
- To investigate if single-nucleotide polymorphisms (SNPs) associated with myocardial infarction (MI) or CAD are also associated with IS.
- To test the hypothesis of shared genetic etiology between MI/CAD and IS.
Main Methods:
- Meta-analysis of 11 MI/CAD-associated SNPs across 9 studies (6865 cases, 11395 controls).
- SNPs were genotyped or imputed; logistic regression and inverse variance weighted random-effect models were used.
Main Results:
- None of the evaluated SNPs showed a significant association with overall IS or major stroke subtypes after adjusting for multiple comparisons.
- The study possessed sufficient power to detect moderate odds ratios (e.g., 1.09 for IS, 1.20 for subtypes).
Conclusions:
- Major genetic loci for MI risk do not appear to confer a similar magnitude of risk for overall IS.
- Disparate underlying biological mechanisms may differentiate acute ischemic coronary and cerebrovascular events.
- The possibility of moderate associations with specific IS subtypes cannot be excluded.
Background And Purpose:
Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS.
Methods:
Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model.
Results:
Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons.
Conclusions:
Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.
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