文章摘要
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,2019,(5):756~761
中国人群冠心病相关基因的精细定位研究
Fine mapping of coronary heart disease associated genes in Chinese population
投稿时间:2019-01-13  
DOI:10.7655/NYDXBNS20190528
中文关键词: 冠心病  易感位点  靶向测序  中国人群
英文关键词: coronary heart disease  susceptibility loci  targeted sequencing  Chinese population
基金项目:国家自然科学基金重大项目(81390543);江苏高校品牌专业建设工程资助项目(PPZY2015A067);江苏高校优势学科建设工程资助项目
作者单位
蒋 祝 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
孙 洁 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
蒋 涛 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
朱 猛 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
李志华 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
程 越 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
陈梦茜 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
戴俊程 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
沈 冲 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
胡志斌 南京医科大学公共卫生学院流行病与卫生统计学系江苏 南京 211166 
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中文摘要:
      目的:全基因组关联研究(genome?wide association studies,GWASs)已发现了多个冠心病(coronary heart disease,CHD)易感区域。然而,这些易感区域内的致病基因和真正致病位点尚不清楚。本研究旨在通过对报道的易感区域进行靶向测序来鉴定CHD相关基因和变异。方法:基于GWAS Catalog数据库筛选满足GWAS显著水平的CHD易感位点,经过多个数据库评估和基因功能检索,系统筛选了19个CHD易感区域内的关键基因。针对上述易感基因,在192例中国人群冠心病患者和192例健康对照中进行捕获测序。通过Logistic回归和计数法评估常见、罕见变异与CHD发生之间的关联。对于鉴定的CHD相关变异,采用功能注释和表达数量性状(eQTL)分析来评估其潜在的生物学功能。结果:5个常见变异关联P值<0.05,功能注释表明其中rs12970与心血管组织中APOA1表达增加显著相关。鉴定了3个功能性罕见变异:WDR35 rs139543775、KLHDC10 rs60941031、CTSH rs3129。结论:通过在GWAS报道的区域中进行精细定位研究,为CHD遗传研究提供了新线索,但是仍需进一步大样本研究和功能实验来验证。
英文摘要:
      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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