Fine mapping of coronary heart disease associated genes in Chinese population
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    Abstract:

    Objective:Genome-wide association studies(GWASs)have identified several coronary heart disease(CHD)susceptibility loci. However,the pathogenic genes and real causal variants in these susceptible regions remain undetected. This study aims to identify CHD associated genes and variants through performing targeted sequencing in susceptible regions reported. Methods:We screened SNVs that were significantly associated with CHD risk base on GWAS Catalog,than selected 19 important genes in CHD susceptible regions by evaluating in databases and retrieving the gene function systematically. Targeted exon sequencing of 19 CHD susceptibility genes was performed within 192 Chinese CHD cases and 192 controls. Association between common/rare variants and CHD risk was evaluated by logistic regression and counting method. Further,for our identified novel CHD-related variants,functional annotation and expression Quantitative Trait Loci(eQTL)analysis were adopted to assess their potential biological functions. Results:There were 5 common variants with P < 0.05,and the eQTL analysis indicated that rs12970 was significantly associated with the increased expression of APOA1 in cardiovascular tissues. Moreover,we identified 3 rare functional variants:WDR35 rs139543775,KLHDC10 rs60941031,CTSH rs3129. Conclusion:This study provides deeper insight into the CHD genetic research by conducting fine mapping in GWAS reported regions. Further validation studies and functional experiments are needed to validate our findings.

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蒋 祝,孙 洁,蒋 涛,朱 猛,李志华,程 越,陈梦茜,戴俊程,沈 冲,胡志斌.中国人群冠心病相关基因的精细定位研究[J].南京医科大学学报(自然科学版英文版),2019,(5):756-761.

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History
  • Received:January 13,2019
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  • Online: May 31,2019
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