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.
基金:
National Key Research and Development Program of China [2017YFC0909400]; National Natural Science Foundation of China [91439203, 81630010, 91839302]; Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]; Fundamental Research Funds for the Central Universities [2015ZDTD044, 2016JCTD117]; Graduate Innovation and Entrepreneurship Funds of Huazhong University of Science and Technology [2018JYCXJJ004]; Tongji Hospital Clinical Research Flagship Program [2019CR207, 2019YBKY019]
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
通讯作者:
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
推荐引用方式(GB/T 7714):
Xiao Lei,Wu Dongyang,Sun Yang,et al.Whole-exome sequencing reveals genetic risks of early-onset sporadic dilated cardiomyopathy in the Chinese Han population[J].SCIENCE CHINA-LIFE SCIENCES.2022,65(4):770-780.doi:10.1007/s11427-020-1951-4.
APA:
Xiao, Lei,Wu, Dongyang,Sun, Yang,Hu, Dong,Dai, Jiaqi...&Wang, Daowen.(2022).Whole-exome sequencing reveals genetic risks of early-onset sporadic dilated cardiomyopathy in the Chinese Han population.SCIENCE CHINA-LIFE SCIENCES,65,(4)
MLA:
Xiao, Lei,et al."Whole-exome sequencing reveals genetic risks of early-onset sporadic dilated cardiomyopathy in the Chinese Han population".SCIENCE CHINA-LIFE SCIENCES 65..4(2022):770-780