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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (3): 432-437. doi: 10.19723/j.issn.1671-167X.2020.03.006

• 论著 • 上一篇    下一篇

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

郑鸿尘1,薛恩慈1,王雪珩1,陈曦1,王斯悦1,黄辉1,江锦1,叶莺2,黄春兰3,周筠4,高文静1,余灿清1,吕筠1,吴小玲3,黄小明3,曹卫华1,严延生2,吴涛(),李立明1   

  1. 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
  • 收稿日期:2020-02-16 出版日期:2020-06-18 发布日期:2020-06-30
  • 通讯作者: 吴涛 E-mail:twu@bjmu.edu.cn
  • 基金资助:
    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)

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

Hong-chen ZHENG1,En-ci XUE1,Xue-heng WANG1,Xi CHEN1,Si-yue WANG1,Hui HUANG1,Jin JIANG1,Ying YE2,Chun-lan HUANG3,Yun ZHOU4,Wen-jing GAO1,Can-qing YU1,Jun LV1,Xiao-ling WU3,Xiao-ming HUANG3,Wei-hua CAO1,Yan-sheng YAN2,Tao WU(),Li-ming LI1   

  1. 1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
    2. Department of Local Disease Control and Prevention, Fujian Provincial Center for Disease Control and Prevention, Fuzhou 350001, China
    3. Department of Hygiene, Nanjing County Center for Disease Control and Prevention, Nanjing 363600 Fujian, China
    4. Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
  • Received:2020-02-16 Online:2020-06-18 Published:2020-06-30
  • Contact: Tao WU E-mail:twu@bjmu.edu.cn
  • Supported by:
    Special Fund for Health Scientific Research of Public Welfare(201502006);Training Project for Young Backbone Talents in Fujian Health System(2014-ZQN-ZD-7)

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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1 563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。

关键词: 遗传度, 家系研究, 静息心率, 高血压, 糖尿病

Abstract:

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 1 563 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 account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120-1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181-0.788, P<0.05).Conclusion: Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.

Key words: Heritability, Pedigree, Resting heart rate, Hypertension, Diabetes

中图分类号: 

  • R181.3+3

表1

研究对象基本人口学特征"

Characteristics Male Female Total P
Gender, n(%) 681 (39.4) 882 (60.6) 1 563 (100)
Age/years, x?±s 58.4 ±13.0 56.4±13.4 57.2±13.2 <0.05
Marriage status, n(%) <0.05
Married 632 (92.8) 768 (87.1) 1400 (89.6)
Divorce/Widowed 29 (4.3) 96 (10.9) 125 (8.0)
Unmarried 20 (2.9) 18 (2.0) 38 (2.4)
Education level, n(%) <0.05
Below primary 115 (16.9) 417 (47.3) 532 (34.0)
Primary 221 (32.5) 222 (25.2) 443 (28.3)
Junior high 222 (32.6) 149 (16.9) 371 (23.7)
Senior high 101 (14.8) 66 (7.5) 167 (10.7)
College or above 22 (3.2) 28 (3.2) 50 (3.2)
Occupation, n(%) <0.05
Farmer or worker 371 (54.5) 368 (41.7) 739 (47.3)
Administrator or professional 30 (4.4) 28 (3.2) 58 (3.7)
Retiree or student 115 (16.9) 51 (5.8) 166 (10.6)
Household 120 (17.6) 99 (11.2) 219 (14.0)
Other 45 (6.6) 336 (38.1) 381 (24.4)
Smoking status, n(%) <0.05
Current smoking 283 (41.6) 22 (2.5) 305 (19.5)
Ex-smoking 94 (13.8) 3 (0.3) 97 (6.2)
Never smoking 304 (44.6) 857 (97.2) 1161 (74.3)
Alcohol consumption, n(%) <0.05
Current drinking 137 (20.1) 29 (3.3) 166 (10.6)
Ex-drinking 31 (4.6) 6 (0.7) 37 (2.4)
Never drinking 513 (75.3) 847 (96.0) 1360 (87.0)
Hypertension, n(%) 367 (53.9) 402 (45.6) 769 (49.2) <0.05
Diabetes, n(%) 88 (12.9) 69 (7.8) 157 (10.0) <0.05
Dyslipidemia, n(%) 347 (51.0) 359 (40.7) 706 (45.2) <0.05
BMI/(kg/m2), x?±s 23.4±3.5 23.3±3.2 23.4±3.3 0.56
SBP/mmHg), x?±s 139.6±20.5 137.3±22.3 138.3±21.5 <0.05
DBP (mm Hg), x?±s 82.2±11.3 78.2±11.2 79.9±11.4 <0.05
Resting heart rate/ (/min), x?±s 78.3±11.2 77.9±10.2 78.1±10.6 0.47

表2

家系构建基本信息"

Generation Pedigrees Total family members Investigated members Average investigated members per pedigree Investigation ratio/%
2 240 751 503 2.10 70.0
3 186 1 575 814 4.38 51.7
4 23 380 191 8.30 50.3
5 2 50 23 11.5 46.0
7 1 62 32 32 51.6

表3

静息心率及常见慢性病单表型遗传度"

Variables Effect of covariatesa Heritability (95%CI) P
Resting heart rate 0.022 0.263 (0.120-0.407) <0.001
Hypertension - 0.404 (0.135-0.673) 0.001
Diabetes - 0.272 (-0.164-0.708) 0.11
Dyslipidemia - 0.799 (0.590-1.000) <0.001
SBP 0.187 0.379 (0.213-0.545) <0.001
DBP 0.069 0.306 (0.155-0.458) <0.001
Fasting glucoseb 0.054 0.393 (0.244-0.543) <0.001
Total cholesterolb 0.034 0.452 (0.306-0.598) <0.001
Triglycerideb 0.040 0.568 (0.429-0.707) <0.001
HDL-Cb 0.037 0.852 (0.741-0.964) <0.001
LDL-C 0.042 0.387 (0.236-0.538) <0.001

表4

静息心率及常见慢性病双表型遗传度"

Variables Environmental correlation Pa Genetic correlation (95%CI) Pb Pc Phenotypic correlation Pd
Hypertension 0.163 0.13 -0.086 (-0.515-0.343) 0.70 <0.05 0.080 <0.05
Diabetes -0.108 0.41 0.795 (0.120-1.000) <0.05 0.31 0.159 <0.05
Dyslipidemia 0.297 0.08 -0.170 (-0.467-0.128) 0.25 <0.05 0.034 0.29
SBP 0.126 0.13 -0.188 (-0.486-0.110) 0.30 <0.05 0.026 0.32
DBP 0.344 <0.05 -0.214 (-0.625-0.197) 0.27 <0.05 0.187 <0.05
Fasting glucosee 0.068 0.40 0.485 (0.181-0.788) <0.05 <0.05 0.203 <0.05
Total cholesterole 0.100 0.23 -0.151 (-0.463-0.161) 0.34 <0.05 0.011 0.68
Triglyceridee 0.185 <0.05 -0.129 (-0.413-0.156) 0.37 <0.05 0.054 <0.05
HDL-Ce -0.015 0.91 0.022 (-0.204-0.249) 0.85 <0.05 0.005 0.83
LDL-C 0.051 0.52 -0.171 (-0.505-0.162) 0.32 <0.05 -0.021 0.41
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CN 11-4691/R
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