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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (3): 432-437. doi: 10.19723/j.issn.1671-167X.2020.03.006

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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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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

CLC Number: 

  • R181.3+3

Table 1

Demographic characteristics of participants"

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

Table 2

Basic information of pedigree reconstruction"

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

Table 3

Univariate heritability of resting heart rate and common chronic diseases"

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

Table 4

Bivariate heritability of resting heart rate and common chronic diseases"

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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