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GWAS 对心房颤动和心房颤动相关卒中的贡献:病理生理学意义。

GWAS contribution to atrial fibrillation and atrial fibrillation-related stroke: pathophysiological implications.

机构信息

Molecular Oncology & Viral Pathology Group-Research Center, Portuguese Institute of Oncology, Edifício Laboratórios. 4° piso, Rua Dr António Bernardino de Almeida, 4200-4072 Porto, Portugal.

FMUP, Faculty of Medicine, Porto University, Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal.

出版信息

Pharmacogenomics. 2019 Jul;20(10):765-780. doi: 10.2217/pgs-2019-0054. Epub 2019 Aug 1.

Abstract

Atrial fibrillation (AF) and stroke are included in a group of complex traits that have been approached regarding of their study by susceptibility genetic determinants. Since 2007, several genome-wide association studies (GWAS) aiming to identify genetic variants modulating AF risk have been conducted. Thus, 11 GWAS have identified 26 SNPs (p < 5 × 10), of which 19 reached genome-wide significance (p < 5 × 10). From those variants, seven were also associated with cardioembolic stroke and three reached genome-wide significance in stroke GWAS. These associations may shed a light on putative shared etiologic mechanisms between AF and cardioembolic stroke. Additionally, some of these identified variants have been incorporated in genetic risk scores in order to elucidate new approaches of stroke prediction, prevention and treatment.

摘要

心房颤动(AF)和中风属于一组复杂的特征,已经通过易感遗传决定因素来研究它们。自 2007 年以来,已经进行了几项旨在确定调节 AF 风险的遗传变异的全基因组关联研究(GWAS)。因此,11 项 GWAS 已经确定了 26 个 SNP(p < 5 × 10),其中 19 个达到了全基因组显著性(p < 5 × 10)。在这些变体中,有七个也与心源性栓塞性中风相关,三个在中风 GWAS 中达到全基因组显著性。这些关联可能为 AF 和心源性栓塞性中风之间可能存在的共同病因机制提供线索。此外,其中一些已确定的变异已被纳入遗传风险评分中,以阐明中风预测、预防和治疗的新方法。

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