Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Bunkyo-Ku, Japan.
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-Ku, Japan.
Eur J Clin Invest. 2023 Dec;53(12):e14084. doi: 10.1111/eci.14084. Epub 2023 Aug 28.
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.
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.
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 ). We estimated bivariate logistic regression model which contained GRS and CHADS2 score (GRS: p-Value = 7.41 × 10 , CHADS2 score: p-Value <2.0 × 10 ) or CHA2DS2-VASc scores (GRS: p-Value = 2.52 × 10 , CHA2DS2-VASc score: p-Value <2.0 × 10 ).
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.
中风是死亡的主要原因，也是成年人获得残疾的主要原因。心源性栓塞性中风患者的死亡率和复发率也高于其他中风亚型患者。心房颤动（AF）是脑梗死（CI）的主要危险因素。MEGASTROKE 研究确定了 32 个与中风相关的基因位点。然而，很少有研究试图在有 AF 病史的患者中发现新的中风风险变异。我们的总体目标是在 AF 病例中发现新的 CI 风险变异，并探讨其与 CI 风险的关联是否受 CHADS2 和 CHA2DS2-VASc 评分的影响。
我们使用之前全基因组关联研究（GWAS）和无对照的推断数据中的 8181 例 AF 病例进行了与 CI 的关联研究。我们将 AF 病例分为有或无既往 CI 病史的病例，并检查了与 CI 风险的遗传关联。
GWAS 确定了 8 个相关的基因座。这 8 个基因座的遗传风险评分（GRS）与 AF 患者的 CI 显著相关（1.46×10）。我们估计了包含 GRS 和 CHADS2 评分的双变量逻辑回归模型（GRS：p 值=7.41×10，CHADS2 评分：p 值<2.0×10）或 CHA2DS2-VASc 评分（GRS：p 值=2.52×10，CHA2DS2-VASc 评分：p 值<2.0×10）。
我们确定了 8 个潜在与 AF 患者 CI 风险相关的遗传变异，且显著的 GRS 与 CHADS2 或 CHA2DS2-VASc 评分无关。
