Familial aggregation and heritability for cardiovascular risk factors: a family based study in Punjab, India

doi:10.4236/ns.2010.27091

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Vol.2, No.7, 732-736 (2010) Natural Science

http://dx.doi.org/10.4236/ns.2010.27091

Familial aggregation and heritability for cardiovascular

risk factors: a family based study in Punjab, India

Raman Kumar, Badaruddoza*

Department of Human Genetics, Guru Nanak Dev University, Amritsar, India; *Corresponding Author: [email protected]

Received 19 March 2010; revised 15 April 2010; accepted 20 April 2010.

ABSTRACT

Background: It is well established that the peo-

ple with elevated SBP, DBP, BMI and WHR are

more prone to cardiovascular disease. However,

very few studies have focused on the amount of

familial aggregation and heritability of these

cardiovascular risk factors in Indian population.

Therefore, purpose of this study was to inves-

tigate the familial aggregation of blood pres-

sures with respect to certain anthropometric

traits and to determine the relative roles of he-

redity in the etiology of SBP and DBP in a sam-

ple of families with three generations. Methods:

The study has been conducted through house

to house family study among three generations

such as offspring, parent and grandparent in a

scheduled caste community (Ramdasia) in

Punjab. A total of 1400 individuals, constituting

380 families were surveyed for blood pressure,

pulse rate, pulse pressure and anthropometric

measurements to study familial aggregation and

heritability for cardiovascular risk factors. The

analysis represents a multivariate model which

includes the each individual family data for es-

timation of familial correlation and heritability.

Results: All risk factors showed positive familial

correlation but magnitudes are different in va-

rious pairs of combination. Correlations gener-

ally are higher among genetically close relatives

such as brother-sisters or parent-offspring and

are lower among spouses. The estimated heri-

tabilities were 22% for systolic and 27% for dia-

stolic blood pressure, 19% for BMI and 17% for

WHR. Conclusions: These results indicate a

strong familial aggregation of cardiovascular

risk factors such as SBP and DBP in this popu-

lation and also showed that this familial influ-

ence can be detected from anthropometric mea-

surements and genetic closeness. Almost all

anthropometric variables were found to be sig-

nificant with blood pressures among three ge-

nerations.

Keywords: Familial Aggregation; Heritability; Risk

Factors; Ramdasia Population; Punjab

1. INTRODUCTION

There is much epidemiological evidence that environ-

mental cofactors and anthropometric characteristics are

directly and consistently correlated with cardiovascular

diseases in developing countries [1-7]. It has been re-

ported that almost 30% of risk factors for cardiovascular

diseases are accounted by genetic heritability and at least

approximately 70% of risk factors are of familial in na-

ture [8-13]. However, many authors have contradicted

that what extent to which that observed familial aggre-

gation on both systolic and diastolic is due to genetic or

environmental reason. Some authors have argued that

familial aggregation on diastolic blood pressure is more

than systolic blood pressure or vice versa [14]. However,

in India the pattern of risk factors for cardiovascular

diseases are different to cut across the cultural patterns

and geographic regions. Therefore, in Indian context the

paucity of family based information and complex etiol-

ogy of this disease made it difficult for understanding

how these factors contribute to the cardiovascular dis-

eases. Hence, the major purpose of this study was to

investigate the familial aggregation of blood pressures

with respect to certain anthropometric traits and to de-

termine the relative roles of heredity in the etiology of

SBP and DBP in a sample of families with three genera-

tions such as offspring, parent and grandparent in Punjab,

a north Indian state. Our working hypotheses were that

there is familial aggregation of blood pressure in the

studied families and the association of blood pressure in

first degree relatives is more than spouse pairs.

2. MATERIALS AND METHODS

For the present study the population included 1400 indi-

R. Kumar et al. / Natural Science 2 (2010) 732-736

733

viduals constituting 380 families with three generations.

Individuals in the parental generation (N = 780) range in

age from 30.5 to 60.7 years. The age of offspring (N =

456) range from 9.5 to 26.7 years. The age of the grand-

parent generation (N = 164) range from 52.8 to 85.6

years. All families were recruited from Ramdasia com-

munity (Ramdasia community is socially and education-

ally backward from the rest of the population in Punjab)

to reduce the confounding effect ethnically determined

genetic differences. For recruitment of the subjects fam-

ily history of heart disease was not the criteria, however,

randomly selected families exhibiting a broad cross se-

lection of cardiovascular risk factor levels.

2.1. Phenotypes Measurements

This study was approved by the Ethics Review Commit-

tee of Guru Nanak Dev University, Amritsar, India and

written consent was obtained from all the participants.

Comprehensive and elaborated questionnaires related

health, life style, demographic features, socio-economic

status and family history were completed by the partici-

pants before physical measurement. Blood pressure was

measure on the right arm of the subjects in a sitting posi-

tion after 10 minutes of rest using a mercury sphygmo-

manometer and a stethoscope with an accuracy of 2 mm

Hg by following the recommendations of American

Heart Association [15]. On the basis of circumference of

the participants arm, a regular adult or large or medium

cuff has been chosen. Systolic and diastolic blood pres-

sures were defined at the first and fifth phases of Korot-

koff sounds respectively. The pulse rate was measured

for 60 seconds. The average of two measurements was

used as the estimates of SBP and DBP in the present

analysis. Mean arterial blood pressure (MBP) was cal-

culated as DBP + (SBP-DBP)/3 [16]. The pulse pressure

was calculated as SBP-DBP.

The other anthropometric measurements were taken

from each individual include height, weight, five cir-

cumferences (chest, waist, hip, arm and calf) and biceps

and triceps skinfolds. All measurements were taken with

standard anthropometric techniques [17-18]. Body mass

index (BMI) and waist to hip ratio were defined as

weight/height2 (kg/m2) and waist circumference divided

by hip circumferences respectively.

2.2. Statistical Methods

All statistical analyses were performed using SPSS

software. The p < 0.05 level was selected as the criterion

of statistical significance. Heritability estimation was

done from regression of offspring on parents.

3. RESULTS

Table 1 shows the summary of data for offspring, parent

and grandparent generations with both sexes. The mean

ages and standard deviations for different generations are:

18.00 ± 5.12 (male offspring), 17.63 ± 4.95 (female off-

spring), 41.19 ± 9.12 (male parents), 38.05 ± 9.16 (fe-

male parents), 67.52 ± 9.10 (male grandparents) and

62.46 ± 8.72 (female grandparents). In general, maxi-

mum mean values of anthropometric measurements such

as height, weight and calf circumference for male parent

generation; BMI, chest, hip and arm circumferences,

biceps and triceps skinfolds for female parent generation;

waist circumference, WHR for female grandparent gen-

eration have been observed in the present analysis. The

maximum SBP, DBP, MBP, pulse rate and pressure have

been found in female grandparent generation. On aver-

age, offspring generations have lower mean values of

almost all measured phenotypes. As shown in the Table

2 all the means of the measured variables have signifi-

cant differences (p < 0.001) between different intra-gen-

erations for all measured variables. However, age, DBP,

calf and hip circumferences, and WHR have found max-

imum intra-generational differences.

Estimates of familial correlations among household

members and estimated sample size are presented in

Table 3. All correlations are positive and maximum fa-

milial correlations for almost all the traits were found in

close genetically related brother-sister combination. The

lowest familial correlations for all the traits were found

in spouses. The familial correlations for SBP and DBP

are also significantly higher between father-male off-

spring combination. However, the stronger correlations

were found in various traits among different combina-

tions such as for biceps skinfold, chest circumference,

pulse pressure between father-male offspring; for arm

circumference between father-female offspring; for BMI,

WHR and pulse rate between mother-female offspring.

Therefore, these risk factors showed the patterns of fa-

milial correlation which were stronger among more ge-

netic control relationship and lower in spouse.

Table 4 shows estimated genetic component of vari-

ance and heritability for cardiovascular risk factors in

this population. The genetic variance included only the

additive genetic variance and these are significantly

greater than zero for all the risk factors. The genetic ef-

fect of these risk factors may be assumed from the

square root of these variances. For SBP the genetic effect

is 10.56 mm Hg and it contributes 22% (heritability) of

the variation in systolic blood pressure. For diastolic

blood pressure the genetic effects is 7.28 mmHg and it

contributes 27% of the variation in this population.

However, the contributions of genetic effects of other

variables such as pulse rate, pulse pressure, body mass

index (BMI), waist to hip ratio (WHR), biceps and tri-

ceps skinfolds, arm and calf circumferences are 10.03

minutes (heritability 10%), 8.75 mm (heritability 30%),

R. Kumar et al. / Natural Science 2 (2010) 732-736

734

Table 1. Descriptive statistics of measured phenotypes between among different generations.

Male Offspring Female Offspring Male Parent Female Parent Male Grandparent Female Grandparent

Variables Mean ±

Inter-

quartile

range

Mean ±

Inter-qua-

rtile range

Mean ±

Inter-

quartile

range

Mean ±

Inter-

quartile

range

Mean ±

Inter-

quartile

range

Mean ±

Inter-

quartile

range

Age (yrs) 18.00 ± 5.12 7.00-35.00 17.63 ± 4.95 7.00-30.00 41.19 ± 9.1221.00-67.0038.05 ± 9.1620.00-65.0067.52 ± 9.10 46.00-96.00 62.46 ± 8.7240.00-85.00

Height (cm) 157.79 ± 10.6 101.50 − 183.0 150.21 ± 9.98 105.00 − 172.00 167.71 ± 6.44148.70 − 186.1154.12 ± 5.5136.20 − 172.3164.96 ± 7.1 142.7 − 183.3 152.13 ± 6.23131.00 − 168.0

Weight (kg) 47.43 ± 11.42 14.00 − 92.00 42.87 ± 10.56 15.00 − 89.0065.19 ± 10.8237.00 − 9859.25 ± 11.932.00 − 105.0055.68 ± 10.2 40.00 − 93.30 56.49 ± 10.5830.00 − 90.00

BMI (kg/m2) 18.42 ± 3.56 11.26 − 35.57 18.77 ± 3.82 10.41 − 36.8523.10 ± 3.7513.54 − 34.5124.87 ± 4.7014.67 − 45.3720.29 ± 4.05 13.71 − 31.66 24.33 ± 4.6714.07 − 37.94

Chest circum(cm) 80.19 ± 9.12 52.50 − 116.40 77.32 ± 8.99 52.70 − 112.0094.31 ± 8.5273.00 − 120.2094.81 ± 8.4570.00 − 130.0090.23 ± 8.49 77.6 − 113.00 94.65 ± 8.2071.00 − 119.00

Waist circum(cm) 75.17 ± 10.35 47.80 − 115.00 72.43 ± 9.68 46.5 − 113.0094.36 ± 8.4661.60 − 129.9096.81 ± 9.9961.00 − 136.0089.24 ± 10.3 65.40 − 121.0 97.98 ± 9.9965.00 − 127.00

Hip circum. (cm) 82.16 ± 9.42 52.00 − 112.00 81.78 ± 8.48 47.00 − 121.5094.12 ± 7.8873.33 − 122.4094.66 ± 9.0172.50 − 130.0087.89 ± 8.11 76.30 − 106.4 93.94 ± 9.8472.00 − 121.30

WHR 0.91 ± 0.06 0.71 − 1.10 0.86 ± 0.070 0.69 − 1.09 1.00 ± 0.071.253 − 0.7591.00 ± 0.110.07 − 1.881.01 ± 0.09 0.804 − 1.269 1.04 ± 0.1430.10 − 1.294

Arm circum. (cm) 22.87 ± 4.39 13.90 − 37.80 21.97 ± 3.51 13.80 − 33.8027.11 ± 3.2818.40 − 37.0026.78 ± 3.4818.50 − 38.5024.00 ± 3.56 17.30 − 33.40 26.08 ± 3.8217.20 − 35.50

Calf circum (cm) 28.32 ± 4.13 18.00 − 42.00 27.13 ± 3.64 17.40 − 41.5031.87 ± 3.3921.00 − 41.8030.63 ± 3.6417.80 − 42.5028.85 ± 3.64 16.40 − 37.60 28.96 ± 3.6922.20 − 37.30

Biceps skinfold

(mm) 6.30 ± 2.57 3.00 − 17.00 7.66 ± 3.42 3.00 − 32.007.84 ± 2.912.00 − 20.0010.58 ± 4.053.00 − 31.005.89 ± 3.04 2.00 − 17.00 9.56 ± 4.383.00 − 29.00

Triceps skinfold

(mm) 9.94 ± 4.34 4.00 − 17.00 13.50 ± 4.31 4.00 − 42.0012.49 ± 4.483.00 − 32.0020.10 ± 6.733.00 − 31.009.72 ± 5.07 3.00 − 28.00 18.37 ± 7.844.00 − 4.00

SBP (mm/Hg) 116.47 ± 10.5 90.00 − 150 111.59 ± 9.22 80.00 − 140.00128.09 ± 9.2090.00 − 210.00122.98 ± 9.480.00 − 190.00136.96 ± 9.7 100.0 − 220.0 144.57 ± 10.190.00 − 240.00

DBP (mm/Hg) 76.50 ± 7.29 55.00 − 110.00 73.95 ± 6.70 50.00−90.0082.11 ± 7.8060.00 − 120.0078.73 ± 8.1560.00 − 120.0082.42 ± 8.08 50.00 − 120.0 85.17 ± 9.9750.00 − 120.00

MBP (mm/Hg) 89.80 ± 7.68 66.00 − 120.00 86.41 ± 6.79 63.33 − 106.6697.39 ± 9.1970.00 − 15093.45 ± 9.1866.66 − 140.00100.26 ± 9.6 66.66 − 153.3 104.76 ± 10.063.33 − 160.00

Pulse rate 81.96 ± 8.02 20.00 − 90.00 85.37 ± 8.67 60.00 − 121.0082.91 ± 9.7860.00 − 120.0085.58 ± 10.860.00 − 90.0084.48 ± 8.99 65.00 − 140.0 85.79 ± 8.2560.00 − 113.00

Pulse pressure 40.49 ± 8.76 54.00 − 132.00 37.87 ± 7.43 20.00 − 60.0046.13 ± 10.7710.00 − 90.0044.29 ± 10.820.00 − 95.0055.16 ± 9.37 10.00 − 20.00 59.14 ± 9.6120.00 − 130.00

Table 2. T-values with 95% confidence level between intra-generational differences of mean values for all measured phenotypes.

Variables t P 95% confidence level of the difference

Age (yrs) 4.715 < 0.005 18.55-63.05

Height (cm) 54.37 < 0.000 150.36-165.28

Weight (kg) 16.49 < 0.000 45.99-62.97

BMI (kg/m2) 18.67 < 0.000 18.65-24.61

Chest circumference (cm) 27.62 < 0.000 80.34-96.82

Waist circumference (cm) 19.19 < 0.000 75.92-99.40

Hip circumference (cm) 36.09 < 0.000 82.74-95.43

WHR 34.29 < 0.000 0.89-1.04

Arm circumference (cm) 28.16 < 0.000 22.53-27.06

Calf circumference (cm) 42.33 < 0.000 22.53-27.06

Biceps skinfold (mm) 10.72 < 0.000 6.06-9.88

Triceps skinfold (mm) 7.93 < 0.001 9.48-18.56

SBP (mm/Hg) 25.12 < 0.000 113.86-139.82

DBP (mm/Hg) 46.78 < 0.000 75.83-84.19

MBP (mm/Hg) 34.43 < 0.000 88.24-102.48

Pulse rate 160.52 < 0.000 83.35-86.29

Pulse pressure 12.65 < 0.000 37.87-59.16

Table 3. Estimates of familial correlation for cardiovascular risk factors.

Variables BMI WHRBISFTRISFAC CC PR PP SBP DBPMBP

Spouse (n = 312) 0.09 0.08 0.05 0.05 0.12 0.07 0.08 0.07 0.04 0.050.06

Father-male offspring (n = 270) 0.21 0.12 0.16 0.02 0.11 0.18 0.07 0.13 0.31 0.300.25

Father-female offspring (n = 186) 0.15 0.12 0.12 0.05 0.19 0.12 0.07 0.08 0.21 0.200.20

Mother-male offspring (n = 270) 0.23 0.14 0.01 0.04 0.18 0.10 0.07 0.04 0.17 0.150.14

Mother-female offspring (n = 186) 0.29 0.12 0.03 0.06 0.12 0.13 0.18 0.04 0.20 0.180.16

Brother-sister (n = 186) 0.38 0.31 0.15 0.15 0.15 0.12 .21 0.14 0.34 0.310.30

Grandfather-male 0ffspring (n = 66)0.12 0.07 0.07 0.08 0.03 0.14 0.05 0.11 0.16 0.190.19

Grandfather-female (n = 66)

offspring 0.12 0.13 0.12 0.02 0.18 0.12 0.10 0.02 0.13 0.140.14

Grandmother-male offspring (n = 99)0.10 0.10 0.08 0.06 0.14 0.02 0.0 0.06 0.13 0.170.16

Grandmother-female offspring (n =

99) 0.12 0.11 0.13 0.03 0.14 0.09 0.02 0.12 0.14 0.150.13

BMI = Body mass index; WHR = Waist-Hip ratio; AC = Arm circumference; CC = Calf circumference; BISF = Biceps skinfold; TRISF = Triceps

skinfold; SBP = Systolic blood pressure; DBP = Diastolic blood pressure; MBP = Mean arterial blood pressure; PR = Pulse rate; PP = Pulse pressure.

R. Kumar et al. / Natural Science 2 (2010) 732-736

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Table 4. Estimated genetic component of variance and herita-

bility for cardiovascular risk factors.

Risk Factors Genetic Variance Heritability

SBP (mm/Hg) 111.72 22%

DBP (mm/Hg) 53.14 27%

MBP (mm/Hg) 58.94 35%

Pulse rate 100.61 10%

Pulse pressure 76.56% 30%

BMI (kg/m2) 12.67 19%

WHR 0.05 17%

Biceps skinfold (mm) 6.60 21%

Triceps skinfold (mm) 18.83 14%

Arm circumference (cm) 19.36 12%

Chest circumference

(cm) 17.05 35%

3.54 kg/m2 (heritability 19%), 0.22 (heritability 17%),

2.56 mm (heritability 21%), 4.33 mm (heritability 14%),

4.4 cm (heritability 12%) and 4.13 cm (heritability 35%)

respectively in this population.

4. DISCUSSION

The analysis from the present studies of three genera-

tions families in Punjab, a north Indian state have dem-

onstrated strong familial aggregation of BMI, WHR,

SBP and DBP for cardiovascular risk factors. The close

genetic relationship such as parent-offspring, brother-

sister correlations were significantly higher (p < 0.05)

than non-genetic or distant genetic relationship such as

spouses and grandparents. Overall, heritabilities were

estimated to be 22% for SBP, 27% for DBP, 19% for

BMI, 17% for WHR and 21% biceps skinfold. Therefore,

the present observation suggested that genetically more

close relatives have greater chance to aggregate cardio-

vascular risk factors than non-genetical and distant rela-

tives. Many previous studies have also supported this

hypothesis [4,7,10-12,19-21]. The present heritability

analysis represents the additive effects of genes. The

greater range of heritability for different cardiovascular

risk factors have suggested a greater genetic influences

in the familial aggregation of SBP, DBP, pulse pressure,

BMI, chest circumference and biceps skinfold. However

the sample size of three generations strengthens the sta-

tistical power to identify the association of cardiovascu-

lar risk factors with different relationships.

In this context, the present population due to its ho-

mogeneous nature provides a good opportunity to assess

the familial determinants of cardiovascular risk factors.

Families in this population are sufficiently large and

joint in addition to that physical environment and diet

contrast are also almost similar. In conclusion, our data

suggest a significant familial aggregation of cardiovas-

cular risk factors for SBP, DBP, BMI and WHR.

5. ACKNOWLEDGEMENTS

First author (RK) is thankful to the University Grants Commission,

Government of India, for providing Rajiv Gandhi National Fellowship

(No. F.16-31/2006 /SA-II) in the Department of Human Genetics, Guru

Nanak Dev University, Amritsar, Punjab, India.

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