Genetic risk score of cerebral infarction in atrial fibrillation genome-wide association study
Yusuke Ebana1, Lian Liu2, Kensuke Ihara2
1Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Bunkyo-Ku, Japan.
Insights
This study identified eight novel genetic variants associated with cerebral infarction (CI) risk in atrial fibrillation (AF) patients. The genetic risk score was significant and independent of clinical risk factors.
Area of Science:
- Genetics
- Cardiology
- Neurology
Background:
- Stroke is a major cause of death and disability, with cardiogenic embolic stroke having higher mortality rates.
- Atrial fibrillation (AF) is a significant risk factor for cerebral infarction (CI), a type of stroke.
- Previous large-scale studies identified stroke risk loci, but few focused on novel variants in AF patients.
Purpose of the Study:
- To identify novel CI risk variants specifically in AF cases.
- To investigate whether identified genetic associations with CI risk are influenced by CHADS2 and CHA2DS2-VASc scores.
Main Methods:
- Genome-wide association study (GWAS) and imputation data from 8181 AF cases were analyzed.
- AF cases were categorized based on a history of CI.
- Genetic associations with CI risk were examined using logistic regression models.
Main Results:
- Eight associated genetic loci were identified through GWAS.
- A genetic risk score (GRS) derived from these eight loci showed significant association with CI in AF patients (p=1.46×10⁻⁸).
- The GRS was independently associated with CI risk, irrespective of CHADS2 or CHA2DS2-VASc scores.
Conclusions:
- Eight novel genetic variants potentially linked to CI risk in AF patients were discovered.
- A significant genetic risk score was established for CI in AF, independent of established clinical risk factors.
Introduction:
Stroke is a leading cause of death and the primary cause of adult-acquired disability. Patients with cardiogenic embolic stroke also have higher mortality and recurrence rates than patients with other stroke subtypes. Atrial fibrillation (AF) is a major risk factor for cerebral infarction (CI). The large-scale study identified 32 loci in the MEGASTROKE study. However, few studies have attempted to identify novel stroke risk variants in patients with a history of AF. Our overall aim was to identify novel CI risk variants in AF cases and explore whether their associations with the CI risk were affected by the CHADS2 and CHA2DS2-VASc scores.
Methods:
We performed association study with CI using 8181 AF cases in previous genome-wide association study (GWAS) and imputation data without controls. We classified AF cases into those with or without past history of CI, and the genetic associations with the CI risk were examined.
Results:
GWAS identified eight associated loci. The generated genetic risk score (GRS) for the eight loci was significantly associated with CI in patients with AF (1.46 × 10-8 ). We estimated bivariate logistic regression model which contained GRS and CHADS2 score (GRS: p-Value = 7.41 × 10-9 , CHADS2 score: p-Value <2.0 × 10-16 ) or CHA2DS2-VASc scores (GRS: p-Value = 2.52 × 10-10 , CHA2DS2-VASc score: p-Value <2.0 × 10-16 ).
Conclusion:
We identified eight genetic variants that were potentially associated with the risk of CI of AF cases and the significant GRS, whose associations were independent of the CHADS2 or CHA2DS2-VASc score.
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