基于大家系设计的静息心率与常见慢性病双表型遗传度估计  

Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees

作　　者：郑鸿尘 薛恩慈 王雪珩 陈曦 王斯悦 黄辉[1] 江锦 叶莺[2] 黄春兰 周筠 高文静[1] 余灿清[1] 吕筠[1] 吴小玲 黄小明 曹卫华[1] 严延生[2] 吴涛[1] 李立明[1] ZHENG Hong-chen;XUE En-ci;WANG Xue-heng;CHEN Xi;WANG Si-yue;HUANG Hui;JIANG Jin;YE Ying;HUANG Chun-lan;ZHOU Yun;GAO Wen-jing;YU Can-qing;LV Jun;WU Xiao-ling;HUANG Xiao-ming;CAO Wei-hua;YAN Yan-sheng;WU Tao;LI Li-ming(Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China;Department of Local Disease Control and Prevention, Fujian Provincial Center for Disease Control and Prevention, Fuzhou 350001, China;Department of Hygiene, Nanjing County Center for Disease Control and Prevention, Nanjing 363600 Fujian, China;Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100070, China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]福建省疾病预防控制中心地方病防治科,福州350001 [3]福建省漳州市南靖县疾病预防控制中心卫生科,福建南靖363600 [4]首都医科大学附属天坛医院国家神经系统疾病临床医学研究中心,北京100070

出　　处：《北京大学学报（医学版）》2020年第3期432-437,共6页Journal of Peking University:Health Sciences

基　　金：公益性行业科研专项(201502006);福建省卫生系统中青年骨干人才培养项目(2014-ZQN-ZD-7)。

摘　　要：目的:基于福建省南靖县土楼地区大家系,探索静息心率和常见慢性病(高血压、糖尿病、血脂异常)的单表型遗传度和双表型遗传度。方法:研究对象来源于2015年8月至2017年12月福建省漳州市南靖县土楼地区塔下村、曲江村、南欧村募集的张姓居民及其亲属,以及草坂村、图美村、背岭村募集的陈姓居民及其亲属。研究共纳入了来自452个大家系的1563名研究对象。家系关系确定依据为家系信息登记及家谱。采用方差组分模型估计连续性变量的单表型、双表型遗传度,采用易患性-阈值模型估计二分类变量的单表型、双表型遗传度。结果:家系重建纳入了1个七代家系,2个五代家系,23个四代家系,186个三代家系和240个二代家系。研究对象的平均年龄为57.2岁,男性占39.4%。研究对象的高血压、糖尿病、血脂异常患病率分别为49.2%、10.0%、45.2%。单表型遗传度估计显示,静息心率遗传度为0.263(95%CI:0.120~0.407),高血压遗传度为0.404(95%CI:0.135~0.673),血脂异常遗传度为0.799(95%CI:0.590~1)。收缩压、舒张压、血糖、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白的遗传度分别为0.379、0.306、0.393、0.452、0.568、0.852、0.387。双表型遗传度分析显示,静息心率与高血压、糖尿病、舒张压、血糖、甘油三酯存在表型相关性。双表型遗传度显示,静息心率与血糖(遗传相关性0.485,95%CI:0.120~1,P<0.05)和糖尿病(遗传相关性0.795,95%CI:0.181~0.788,P<0.05)具有较强的遗传相关性。结论:静息心率是一个可遗传性状,其与常见慢性病及其相关指标存在相关性。静息心率与糖尿病和血糖值具有较强的遗传相关性,提示静息心率与糖尿病和血糖之间可能存在共同的遗传基础。Objective:To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension,diabetes,and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes.Methods:The study was conducted in Tulou area of Nanjing County,Fujian Province from August 2015 to December 2017.The participants were residents with Zhang surname and their relatives from Taxia Village,Qujiang Village,and Nanou Village or residents with Chen surname and their relatives from Caoban Village,Tumei Village,and Beiling Village.The baseline survey recruited 1563 family members from 452 extended pedigrees.The pedigree reconstruction was based on the family information registration and the genealogy booklet.Univariate and bivariate heritability was estimated using variance component models for continuous variables,and susceptibility-threshold model for binary variables.Results:The pedigree reconstruction identified 1 seven-generation pedigree,2 five-generation pedigrees,23 four-generation pedigrees,186 three-generation pedigrees,and 240 two-generation pedigrees.The mean age of the participants was 57.2 years and the males accounted for 39.4%.The prevalence of hypertension,diabetes,dyslipidemia in this population was 49.2%,10.0%,and 45.2%,respectively.The univariate heritability estimation of resting heart rate,hypertension,and dyslipidemia was 0.263(95%CI:0.120-0.407),0.404(95%CI:0.135-0.673),and 0.799(95%CI:0.590-1),respectively.The heritability of systolic blood pressure,diastolic blood pressure,fasting glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol was 0.379,0.306,0.393,0.452,0.568,0.852,and 0.387,respectively.In bivariate analysis,there were phenotypic correlations between resting heart rate with hypertension,diabetes,diastolic blood pressure,fasting glucose,and triglyceride.After taking resting heart rate into

关 键 词：遗传度 家系研究 静息心率 高血压 糖尿病 

分 类 号：R181.33[医药卫生—流行病学]