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Whole-exome sequencing reveals genetic risks of early-onset sporadic dilated cardiomyopathy in the Chinese Han population

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越:重点期刊

单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Div Cardiol,Dept Internal Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Hubei Key Lab Genet & Mol Mech Cardiol Disorders, Wuhan 430030, Peoples R China
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关键词: DCM genetics case-control risk stratification

摘要:
To reveal genetic risks of early-onset sporadic dilated cardiomyopathy (DCM) patients in the Chinese Han population, we enlisted 363 DCM cases and 414 healthy controls. Whole-exome sequencing and phenotypic characterization were conducted. In total, we identified 26 loss-of-function (LOF) candidates and 66 pathogenic variants from 33 genes, most of which were novel. The deleterious variants can account for 25.07% (91/363) of all patients. Furthermore, rare missense variants in 21 genes were found to be significantly associated with DCM in burden tests. Other than rare variants, twelve common SNPs were significantly associated with an increased risk of DCM in allele-based genetic model association analysis. Of note, in the cumulative risk model, high-risk subjects had a 3.113-fold higher risk of developing DCM than low-risk subjects. Also, DCM in the high-risk group had a younger age of onset than that in the low-risk group. In terms of cardiac function, the mean left ventricular ejection fraction of patients with the deleterious variants was lower than those without (27.73%+/- 10.02% vs. 30.61%+/- 10.85%, P=0.026). To conclude, we mapped a comprehensive atlas of genetic risks in Chinese patients with DCM that might lead to new insights into the mechanisms and risk stratification for DCM.

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出版当年[2021]版:
大类 | 1 区 生物学
小类 | 1 区 生物学
最新[2025]版:
大类 | 1 区 生物学
小类 | 1 区 生物学
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出版当年[2020]版:
Q1 BIOLOGY
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Q1 BIOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Div Cardiol,Dept Internal Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Hubei Key Lab Genet & Mol Mech Cardiol Disorders, Wuhan 430030, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Div Cardiol,Dept Internal Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Hubei Key Lab Genet & Mol Mech Cardiol Disorders, Wuhan 430030, Peoples R China
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