荟萃分析确定了六个心房颤动的新易感性位点。
Meta-analysis identifies six new susceptibility loci for atrial fibrillation.
机构信息
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
出版信息
Nat Genet. 2012 Apr 29;44(6):670-5. doi: 10.1038/ng.2261.
Abstract
Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
摘要
心房颤动是一种高发心律失常，也是中风、心力衰竭和死亡的主要危险因素。我们在欧洲血统个体中进行了一项全基因组关联研究（GWAS），包括 6707 例有和 52426 例无心房颤动的个体。在另外一组欧洲血统个体中鉴定和复制了 6 个新的心房颤动易感性位点，包括 5381 例有和 10030 例无心房颤动的个体（P<5×10(-8)）。在日本人的 GWAS 中，在欧洲人中鉴定的 4 个位点进一步在计算机上复制，包括 843 例有和 3350 例无心房颤动的个体。鉴定的位点提示候选基因，这些基因编码与心肺发育、心脏表达的离子通道和细胞信号分子相关的转录因子。
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1
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JAMA. 2010 Nov 24;304(20):2263-9. doi: 10.1001/jama.2010.1690. Epub 2010 Nov 13.
2
Independent susceptibility markers for atrial fibrillation on chromosome 4q25.染色体 4q25 上与心房颤动相关的独立易感性标志物。
Circulation. 2010 Sep 7;122(10):976-84. doi: 10.1161/CIRCULATIONAHA.109.886440. Epub 2010 Aug 23.
3
CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function.CHAP 是一种新鉴定的 Z 盘蛋白，对于心脏和骨骼肌功能至关重要。
J Cell Sci. 2010 Apr 1;123(Pt 7):1141-50. doi: 10.1242/jcs.063859. Epub 2010 Mar 9.
4
Common variants in KCNN3 are associated with lone atrial fibrillation.常见的 KCNN3 变体与孤立性心房颤动有关。
Nat Genet. 2010 Mar;42(3):240-4. doi: 10.1038/ng.537. Epub 2010 Feb 21.
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Several common variants modulate heart rate, PR interval and QRS duration.几种常见的变体可调节心率、PR 间期和 QRS 持续时间。
Nat Genet. 2010 Feb;42(2):117-22. doi: 10.1038/ng.511. Epub 2010 Jan 10.
6
Genome-wide association study of PR interval.全基因组关联研究 PR 间期。
Nat Genet. 2010 Feb;42(2):153-9. doi: 10.1038/ng.517. Epub 2010 Jan 10.
7
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8
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Nat Genet. 2009 Aug;41(8):876-8. doi: 10.1038/ng.417. Epub 2009 Jul 13.
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10
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Eur Heart J. 2009 Apr;30(7):813-9. doi: 10.1093/eurheartj/ehn578. Epub 2009 Jan 13.
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