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Native American ancestry among Hispanic Whites is associated with higher risk of childhood obesity: a longitudinal analysis of Children’s Health Study data

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Native American ancestry among Hispanic Whites is associated with higher risk of childhood obesity: a longitudinal analysis of Children’s Health Study data

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Native American Ancestry Among Hispanic Whites Is Associated With Higher Risk
Of Childhood Obesity: A Longitudinal Analysis of Children’s Health Study Data

By
Chengke Tang

A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
Partial Fulfillment of the Requirements for the Degree of
MASTER OF SCIENCE
APPLIED EPIDEMIOLOGY AND BIOSTATISTICS

August 2016

I

Abstract

Background: Childhood obesity has become an epidemic in the U.S., and the risk is
particularly dramatic in minority populations such as Hispanic Whites, but the individual
risk susceptibility varies a lot within the Hispanic population. Previous studies have shown
that genetic factors could be one of the major causes of variation in obesity risk among
Hispanics. Since the risk of obesity is also high among Native American populations, our
study aimed to assess the association between Native American ancestry and the risk of
developing obesity among Hispanic White children in the Children’s Health Study (CHS).
Method: 1,718 non-obese children at baseline were included in the analysis. Children were
followed from kindergarten to high school graduation. Height and weight were measured
by a trained technician at every study visit, and obesity was defined as a BMI above 95%
compared to the age and sex-specific Center for Disease Control (CDC) 2000 BMI growth curves.
Socio-demographic status, history of respiratory illness, physical activity, parental
education levels, second hand smoking exposure, and in utero smoking exposure, and other
household characteristics were collected at baseline and every year during the follow-up
using CHS questionnaire. Proportional hazards models were used to analyze the
association between Native American ancestry proportion which was estimated by ancestry
informative markers and the risk of developing obesity during the follow-up. We
categorized Native American ancestry proportion into four groups by Native American
ancestry proportion among Hispanic Whites as <25%, 25-50%, 50-75% and ≥75% groups.
Baseline asthma history, age, overweight, household income, parental education level,
II

physical activity, second-hand smoking, maternal smoking in utero, Spanish questionnaire
usage and follow-up physical activity were adjusted for potential confounders.
Results: Univariate analysis showed that compared to the <25% Native American
admixture, the risk of developing obesity was significantly higher in Hispanic White
children with ≥25% Native American admixture (HR=2.10 95%CI=1.33-3.32). The
association remained significant after adjusting for potential confounders (HR=1.70
95%CI=1.02-2.84). Parental education level and maternal birth place significantly
modified the association between Native American admixture and the risk of developing
obesity during the follow (interaction p=0.023 and 0.04, respectively). Stratified analysis
by parental education levels showed that among children in the group that parental
education level more than collage or technical school, three groups of Hispanic white
children with Native American ancestry 25-50%, 50-75% and ≥75% were associated with
around 2.10 folds lower risk of obesity compared to Hispanic white children with Native
American ancestry <25% (all p<0.130), and it was statistically significant in the 25-50%
group. No significant association was observed among children with parental education
level less than high school. Stratified analysis by maternal birth places showed that among
children whose mother were born in the U.S., the risk of developing obesity for children
with Native American ancestry 25-50%, 50-75% and ≥75% were around 2.10 folds higher
compared to Hispanic white children with Native American ancestry <25% (all p<0.157),
and it was statistically significant in the 25-50% group. But no significant association was
observed between Native American ancestry proportion and the risk of developing obesity
among children with mothers born in Mexico.
III

Conclusion: Native American ancestry ≥25% was associated with higher risk of
developing obesity from age 5 to 8 among Hispanic White Children compare to those with
Native American ancestry <25%. Such association was greater among children with
parental education level lower than high school and with their mothers born in the U.S.
These results indicate that Native American Native American ancestry proportion is a risk
factor for obesity among Hispanic White children, who were known to have higher risk for
obesity compare to other populations. Our results provided inform for future obesity
intervention programs. Early intervention in Hispanic children with high proportion of
Native American ancestry may reduce the overall obesity burden among Hispanic children
and adolescents.

IV

Acknowledgement

I would like to thank my committee chair Dr. Frank Gilliland, for his expertise,
assistance, guidance and patience throughout the process of finishing my project and thesis.
Without your help this paper would not have been possible. I would like to thank my
committee members, Dr. Kiros Berhane and Dr. Rima Habre, for their support, suggestions
and encouragement.

I would like to give my special thanks to Dr. Zhanghua Chen, who provided support
and suggestions during the project and reviewed my thesis many times. I could not finish
my thesis without your help.

Finally, I would like to thank all the staff and faculty in Preventive Medicine
department. Also, I would like to thank all my friends and everyone else who contributing
to my project and thesis; and those who have kept me company during the long walk.

V

Table of Contents
Abstract………………………………………………………………………………..….I
Acknowledgement……………………………………………………………………....IV
Table of Contents………………………………………………………………………..V
List of Tables…………………………………………………………………………....VI
List of Figures……………………………………………………………………...…..VII
Introduction………………………………………………………………………………1
Methods…………………………………..………………………………………………3
Study Population........................................................................................................3
Assessment of Body Mass Index ……………………….……….……………...….4
Assessment of Native American ancestry proportion ………………………....…4
Assessment of Other Questionnaire Variables………………………………...….4
Statistical Analysis………………………………………………………………….5
Results…………………………………………………………………………………….8
Characteristics table………………………………………..………………………8
Association between Native American ancestry proportion and Obesity ..……10
Interaction……………………………………...………………………………….16
Discussion………………………….……………………………………………………21
Reference………………………………………………………………………………..25

VI

List of Tables
Table 1. Univariate associations between child and home characteristics at baseline
and the risk of developing obesity rates from kindergarten through 10th grade ….…9

Table 2. Association between the risk of developing obesity and ethnicity (genetic
ancestry included) among all 1,718 children ……………………………………….....11

Table 3. Association between the risk of developing obesity and Native American
ancestry proportion within 1,096 Hispanic White children ……………….…......….14

Table 4. Association between the risk of developing obesity and Native American
ancestry proportion (NAA≥25% combined) within 1,096 Hispanic children …..….16

Table 5. Stratified analysis of association between the risk of developing obesity and
Native American ancestry proportion by mother’s birth place within 1,096 Hispanic
White children …………………..……………………………...……..…….....……….17

Table 6. Stratified analysis of association between the risk of developing obesity and
Native American ancestry proportion by parental education level within 1,096
Hispanic White children …………..………………...……………..……………….….19

VII

List of Figures
Figure 1. Hazard ratios and 95% confidence intervals of the univariate associations
between Native American ancestry proportion and the risk of developing obesity in
Hispanic Whites, compared to non-Hispanic Whites as the reference group (N=1,718
children)…………………………………………………………………………....……12

Figure 2. Hazard ratios and 95% confidence intervals of associations between Native
American ancestry proportion and the risk of developing obesity in Hispanic Whites
after adjust for potential confounders, compared to non-Hispanic Whites as the
reference group (N=1,718 children) ……………………………………………...……12

Figure 3. Hazard ratios and 95% confidence intervals of the univariate associations
between the risk of developing obesity and Native American ancestry proportion in
Hispanic Whites, compared to Hispanic White with Native American proportion <25%
(N=1,096).………………...…………………………………………………….……..…14

Figure 4. Hazard ratios and 95% confidence intervals of the fully adjusted
associations between the risk of developing obesity and Native American ancestry
proportion in Hispanic Whites, compared to Hispanic White with Native American
proportion <25% (N=1,096).………………………………………...………..………..15

Figure 5. Hazard ratios and 95% confidence intervals of the mother birth place
stratified associations between the risk of developing obesity and Native American
VIII

ancestry proportion in Hispanic Whites, compared to Hispanic White with Native
American proportion <25% (N=1,096).………………………..………………...……18

Figure 6. Hazard ratios and 95% confidence interval of parental education level
stratified association between the risk of developing obesity and Native American
ancestry proportion in Hispanic Whites, compared to Hispanic White with Native
American proportion <25% (N=1,096)………………………..………………..……..20

1

Introduction

The rise of the risk of childhood obesity development in the United States has been
recognized as a significant public health issue over the past few decades with 11.1%
increase of the incidence rate[1]. From 1980 to 2006, the prevalence of obesity increased
almost two folds in children age 2 to 15 years old and more than two folds in children age
16 to 19 years old[2]. Early onset of childhood obesity is a significant risk factor for obesity
and other metabolic diseases during adulthood [2]. In the U.S., more than 30% of children
or adolescents were considered obese based on the Center of Disease Control and
Prevention report in 2012[3]. Both environmental and genetic factors contribute to the
overall obesity risk [4]. Variation of obesity risk among different race/ethnicity groups
have been established in many previous studies [5]. During the past centuries, mankind
broke geographic and cultural boundaries, resulting in the new admixed populations today.
Native American ancestry proportion has been established as a measure of using
informative genetic markers to investigate the proportion of ancestral genes in individuals
based on admixed genetic background. Although the genes of these individuals were
admixed, certain genetic sequences inherited from their ancestry might be considered as
“distinctive”[6]. Higher obesity risk in specific race/ethnicity group such as Hispanics
might be due to the presence of specific DNA sequences that were inherited from the
dominating ancestry group such as Native American, which is one of the ethnicity having
higher risk of obesity[7].

2

Hispanics have a high risk of obesity compared to Caucasians, African Americans
and Asians [8], but the individual susceptibility can vary a lot [9]. Native American
ancestry proportion might explain some of this variation. Previous studies have also
consistently shown that Native American populations have a high risk of obesity and
diabetes [7]. Researchers have hypothesized that one of the potential causes of this high
risk in Native Americans might be a genetic predisposition, or the “thrifty gene”. During
times of famine over many generations, Native Americans built a way to survive by storing
more fat. However, later generations in modern times may store energy in the form of fat
excessively, since they inherited these genes from their ancestors, had lower levels of
physical activity, and substituted proteins for more calorie-dense carbohydrates to a greater
extent [10]. Therefore, we hypothesized that higher proportion of Native American Native
American ancestry proportion is associated with higher risk of obesity. We investigated the
association between Native American ancestry proportion and the risk of developing
obesity among 1,096 Hispanic Whites who were not obese at the study entry of the southern
California Children’s Health Study (CHS) in year 2002 and were followed up from
kindergarten through high school graduation. Also, 622 Non-Hispanic White children were
included in this study as a reference group from the same cohort.

3

Methods

Study Population
In this study, we used data collected from the Children’s Health Study (CHS), which
is one of the largest prospective longitudinal studies to investigate the chronic effects of air
pollution exposures on the health of children living in Southern California starting from
year 1992. In the most recent cohort, 5,026 children at kindergarten or first grade were
enrolled to CHS in 2002 from 13 communities. At the study entry, all parents provided
informed consent. Parent- or self-reported questionnaires were completed annually or bi-
annually during the 10 year follow-up from kindergarten or first grade till high school
graduation. Questionnaires include questions related to socio-demographic status, history
of respiratory illness, physical activity, parental education levels, second hand smoking
exposure, and in utero smoking exposure, and other household characteristics.
Questionnaires were completed by parents from baseline to the 5
th
study year, and by
children themselves from follow-up year 6 (age 10-13) until the end of study [11]. 564
children were excluded due to missing all baseline and follow-up BMI information. 1,841
children from 5 communities were excluded since they did not have complete 10-year
follow-up. 827 obese children at the study entry were further excluded to create a non-
obese cohort for the analysis. 628 children were excluded due to missing Native American
ancestry proportion information. Twelve children from ethnicity groups other than
Hispanic White and non-Hispanic White were also excluded. The final analysis included
622 non-Hispanic White and 1,096 Hispanic White children.

4

Assessment of Body Mass Index
Children enrolled in the CHS had height and weight measured by a trained technician
at every study visit. Technicians followed a standardized protocol that included details on
scale calibration and interaction with the children. These objective measures of height and
weight were used to calculate Body Mass Index (BMI) (weight in kg/height in m
2
). Obesity
and overweight were categorized by comparing BMI to the CDC age-, sex-specific BMI
growth curves[12]. Overweight is defined as a BMI above 85% and below 95% of children
at the same age and sex. Obesity is defined as a BMI above 95% of children at the same
age and sex.

Assessment of Native American ancestry proportion
Native American ancestry proportion was estimated by ancestry informative markers
(AIMs). After picking 233 AIMs, we genotyped them using Illumina Golden Gate assay to
get the ancestry proportion of each subject[13]. Then, Hispanic Whites were categorized
into four groups based on quarters of Native American ancestry proportion (Proportion of
Native American ancestry <25%, 25%-49.9%, 50%-74.9%, and 75% and above). Non-
Hispanic Whites were considered as a reference group.

Assessment of Other Questionnaire Variables
Physical activity was captured by two questions based on the questionnaire. “During
the past 7 days, how many days did your child play an outdoor sport (including both
organized team sports and unorganized sports with friends)?” and “Did your child taken
any of the following exercise classes, lessons, or special programs during the past 12
5

months (outside of school only)?” Classes included dance, aerobics, gymnastics or
tumbling, martial arts and other self-reported sports classes, parent was asked to mark all
that applied. These physical activity questions were asked at baseline and every year during
the follow-up. Follow-up weekly outdoor sports was treated as a time-dependent variable
during the longitudinal analysis. Parental education level was captured by a question on
the last grade in school he/she had completed. Second-hand smoking exposure was
captured by asking the parent if anyone living in the child’s home smokes cigarettes, cigars
or pipes on a daily basis inside the home. Smoking exposure in utero was captured by
asking the parent whether the child’s biological mother smoked while she was pregnant
with this child (including the time when she was pregnant but did not yet know that she
was). History of asthma was evaluated based on yes or no answer from the question that
“whether his/her child had asthma or ever diagnosed as having asthma by a doctor?”

Statistical Analysis
Household income was categorized into three levels, less than $50,000 per year,
$50,000 to $99,999 per year and more than $100,000 per year. Parental education level
was categorized into four levels, less than 12
th
grade, completed grade 12, some college or
technical school and completed 4 years of college and higher. Physical activity information
was captured by two variables, weekly days of outdoor sports in the past year (four
categories: 0, 1-2, 3-4, 5-7 days per week) and number of exercise classes children took in
the past year (0, 1, and more than 2 sport classes). Second-hand smoke exposure was
categorized as no, yes, yes only when children are not present, and maternal smoking in
utero as two categories: no, yes. Asthma and the use of Spanish questionnaire were treated
6

as binary variables. Mother’s birth place was categorized as born in the U.S., Mexico and
other countries. Baseline history of asthma, age, sex, baseline overweight, household
income, parental education level, weekly outdoor sports, number of exercise classes taken
during the prior year, exposure to second-hand smoke and in utero smoking exposure,
mother’s birth place and the use of Spanish questionnaire are adjusted for as potential
confounders. A significant confounder was defined as a variable that changes the
regression coefficient for Native American ancestry proportion by more than 10% after
adjusting for it.

Obesity incidence was defined as the first occurrence of obesity during the follow-up
period. Subjects were censored at the midpoint of the follow-up years before they
developed obesity, or when they were lost to follow-up, or until the end of the study follow-
up. Proportional hazards model was used to assess the association between the risk of
developing obesity. Baseline asthma history, age, overweight status, household income,
parental education levels, weekly outdoor sports, number of exercise classes taken during
the prior year, second-hand smoking, maternal smoking, Spanish questionnaire usage and
follow-up weekly outdoor sports were adjusted for as potential confounders. In the first
analysis, proportional hazards model was used to estimate the relative risk of developing
obesity during the follow-up related with the proportion of Native American ancestry
among Hispanic White children compared to Non-Hispanic White children. In the second
analysis, we restricted our analysis with Hispanic White children and examined the
association between the risk of developing obesity and Native American ancestry
proportion using Native American ancestry proportion <25% as the reference group.
7

Finally, we tested variables including baseline history of asthma, age, sex, baseline
overweight, household income, parental education level, weekly outdoor sports, number of
exercise classes taken during the prior year, second-hand smoking, maternal smoking,
mother birth place and the use of Spanish questionnaire, as effect modifiers of the
association between Native American ancestry proportion and risk of developing obesity
during the follow-up by including them as multiplicative interaction terms in the model.
Likelihood ratio test was used as a global test for these interactions one by one, and
stratified analyses were conducted to evaluate if significant interactions were detected.

All statistical analyses were performed using SAS 9.4 software (SAS, Inc), and
statistical significance was evaluated as a 2-sided test with p-value < 0.05.

8

Results

Descriptive Analysis
Table 1 shows the baseline characteristics of 1,718 CHS participants used in the study.
There were 622 non-Hispanic Whites and 1096 Hispanic Whites, and within Hispanic
Whites, there were 169 participants having Native American ancestry proportion <25%
(NAA <25%), 154 having Native American ancestry proportion between 25%-50% (NAA
25-50%), 254 having Native American ancestry proportion between 50%-75% (NAA 50-
75%) and 519 having Native American ancestry proportion ≥75% (NAA≥75%). Univariate
analysis showed that boys had 1.72 folds higher risk of obesity development compared to
girls (hazard ratio, HR=1.72, 95%CI=1.36-2.17). Children who were overweight at the
study entry had 12.55 folds higher risk of developing obesity during follow-up than
children who were normal weight at the study entry (HR=12.55, 95%CI=8.89-15.92). The
risk of developing obesity for children who used Spanish questionnaire is 1.8 folds higher
compare to children who did not use Spanish questionnaire (HR=1.78, 95%CI=1.41-2.26).

9

Table 1. Univariate associations between child and home characteristics at baseline
and the risk of developing obesity from kindergarten through 10th grade*
Baseline variables N (%) Hazard Ratios 95% CI
Age (Yrs)
5-6 380 (22.12) Ref
6-7 835 (48.60) 1.11 (0.82 – 1.49)
7-8 503 (29.28) 1.20 (0.85 – 1.70)
Sex
Girls 844 (49.13) Ref
Boys 874 (50.87) 1.72 (1.36 – 2.17)
Overweight†
No 1394
(81.14)
Ref
Yes 324 (18.86) 12.55 (9.89–15.92)
Ethnicity
Non-Hispanic Whites 622 (35.95) Ref
Hispanic Whites 1096(64.05) 2.03 (1.55 - 2.65)
Income
Less than $50,000 671 (39.06) Ref
$50,000 to $99,999 472 (27.47) 0.78 (0.59 – 1.03)

$100,000 or more 331 (19.27) 0.41 (0.27 – 0.61)
Missing 244 (14.20)
Education
Less than 12th grade 324 (18.86) Ref
Completed grade 12 310 (18.04) 0.75 (0.51 – 1.03)
Some college or technical
school
587 (34.17) 0.63 (0.47 – 0.86)
More than Completed 4 years
of college
415 (24.16) 0.51 (0.36 – 0.72)
Missing 82 (4.77)
Physical Activity
Weekly days of outdoor sports
0 284 (16.53) Ref
1-2 365 (21.25) 1.30 (0.88 – 1.90)
3-4 510 (29.69) 1.14 (0.79 – 1.65)
5-7 508 (29.57) 1.03 (0.71 – 1.50)
Missing 51 (2.97)
Prior 1-year no. of class
exercises‡

0 1090
(63.45)
Ref
1 425 (24.74) 0.71 (0.53 – 0.96)
≥2 91 (5.30) 0.60 (0.30 – 1.18)
Missing 112 (6.52)
Smoking
Second-hand Smoke exposure
No 1569
(91.33)
Ref
Yes 74 (4.31) 0.96 (0.53 – 1.76)
Yes only when children are not
present
23 (1.34) 1.09 (0.41 – 2.92)
Missing 52 (3.03)
10

Table 1. Univariate associations between child and home characteristics at baseline
and the risk of developing obesity from kindergarten through 10th grade*
(Continued)
Baseline variables N (%) Hazard Ratios 95% CI
Maternal Smoking Exposure In
Utero

No 1562
(90.92)
Ref
Yes 104 (6.05) 1.12 (0.71 – 1.77)
Missing 52 (3.03)
Asthma
No 1385
(80.62)
Ref
Yes 217 (12.63) 1.15 (0.83 – 1.59)
Missing 116 (6.75)
Spanish Questionnaire
No 1280
(74.51)
Ref
Yes 438 (25.49) 1.78 (1.41 – 2.26)
Mother birth place
US 457 (41.70) Ref
Other 53 (4.84) 0.87 (0.47 – 1.60)
Mexico 453 (41.33) 1.50 (1.18 – 1.94)
Missing 133 (12.14)
* Hazard ratios (HR) and 95% confidence intervals (CI) are presented for univariate
association analysis.
† Overweight among children was defined as ≥85 percentile compared to sex-specific CDC
growth curve.
‡ Exercise classes include dance, aerobics, gymnastics or tumbling, martial arts, and other
self-reported exercise classes.

Association between Native American ancestry proportion and Obesity
In the univariate analysis (Table 2), compared to Non-Hispanic White children, the
risk of developing obesity was about the same among Hispanic White children with NAA
<25% (HR=1.06, 95%CI=0.64-1.74), and all the other three groups (NAA≥25%) had
around 2 folds higher risks of developing obesity during the follow-up (HR ranges
from1.97 to 2.40, all p<0.0009).

The association between Native American ancestry proportion and the risk of
developing obesity during the follow-up remained robust after adjusting for baseline
asthma history, age, overweight, household income, parental education level, weekly
11

outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking in utero, Spanish questionnaire usage and follow-up weekly
outdoor sports. Compared to Non-Hispanic Whites, the risk of developing obesity was still
higher for Hispanic children, and the effect was about the same among the group of NAA
<25% (HR=1.03, 95%CI=0.62-1.73), and all the other three groups had around 1.7 folds
higher risks with a range HR:1.57-1.91 (p<0.0477). (See Table 2, Figure 1 and Figure 2).

Table 2. Association between the risk of developing obesity and ethnicity (genetic
ancestry included) among all 1,718 children

*Full model adjusted for asthma, age, overweight, household income, parental education
level, weekly outdoor sports, number of exercise classes taken during the prior year,
second-hand smoking, maternal smoking, Spanish questionnaire and follow-up weekly
outdoor sports. (significance level: 0.05)

Variables
N (%)
Univariate Full Model*
HR 95% CI HR 95% CI
Ethnicity
Non-Hispanic White 622 (35.95) Ref - Ref -
Hispanic White with Native American
ancestry proportion <25%
169 (9.77) 1.06 (0.64-1.74) 1.03 (0.62-1.73)
Hispanic White with Native American
ancestry proportion between 25%-50%
154 (8.9) 2.05 (1.34-3.13) 1.91 (1.22-2.99)
Hispanic White with Native American
ancestry proportion between 50%-75%
254 (14.68) 1.97 (1.38-2.82) 1.57 (1.01-2.44)
Hispanic White with Native American
ancestry proportion ≥75%
519 (30.0) 2.40 (1.79-3.21) 1.66 (1.07-2.56)
12

Figure 1. Hazard ratios and 95% confidence intervals of the univariate associations
between Native American ancestry proportion and the risk of developing obesity in
Hispanic Whites, compared to non-Hispanic Whites as the reference group (N=1,718
children).

Figure 2. Hazard ratios and 95% confidence intervals of associations between Native
American ancestry proportion and the risk of developing obesity in Hispanic Whites
after adjust for potential confounders, compared to non-Hispanic Whites as the
reference group (N=1,718 children)*.

*Model adjusted for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
1.06
2.05
1.97
2.4
0
0.5
1
1.5
2
2.5
3
3.5
Hispanic White <25%
(N=169)
Hispanic White 25%-
50% (N=154)
Hispanic White 50%-
75% (N=254)
Hispanic White ≥75%
(N=519)
Hazard Ratio (95%CI)
Subgroups
1.03
1.91
1.57
1.66
0
0.5
1
1.5
2
2.5
3
3.5
Hispanic White
<25% (N=169)
Hispanic White
25%-50% (N=154)
Hispanic White
50%-75% (N=254)
Hispanic White
≥75% (N=519)
Hazard ratio (95%CI)
Subgroups
13

smoking, maternal smoking, Spanish questionnaire and follow-up weekly outdoor sports.
(significance level: 0.05)

Table 3 shows the association between the risk of developing obesity and Native
American ancestry proportion within 1,096 Hispanic White children. In the univariate
analysis, compared to the group of Hispanic White children with NAA <25%, the risk of
developing obesity was 1.94 folds higher among Hispanic Whites with NAA between 25-
50% (HR=1.94, 95%CI=1.10-3.40), and 1.87 folds higher among Hispanic Whites with
NAA between 50-75% (HR=1.87, 95%CI=1.11-3.13), and 2.26 folds higher among
Hispanic Whites with NAA ≥75% (HR=2.26, 95%CI=1.41-3.62). After adjustment for
asthma, age, overweight, household income, parental education level, weekly outdoor
sports, number of exercise classes taken during the prior year, second-hand smoking,
maternal smoking, Spanish questionnaire usage and follow-up weekly outdoor sports,
compared to the group of Hispanic White children with NAA <25%, the risks of developing
obesity were 1.90 folds higher among Hispanic Whites with NAA between 25-50%
(HR=1.90, 95%CI=1.06-3.39), and 1.53 folds higher among Hispanic Whites with NAA
between 50-75% (HR=1.53, 95%CI=0.86-2.72), and 1.62 folds higher among Hispanic
Whites with NAA ≥75% (HR=1.62, 95%CI=0.92-2.87).

14

Table 3. Association between the risk of developing obesity and Native American
ancestry proportion within 1,096 Hispanic White children
*Model adjusted for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking, Spanish questionnaire and follow-up weekly outdoor sports.
(significance level: 0.05)

Figure 3. Hazard ratios and 95% confidence intervals of the univariate associations
between the risk of developing obesity and Native American ancestry proportion in
Hispanic Whites, compared to Hispanic White with Native American proportion <25%
(N=1,096).

1.94 1.87
2.26
0
0.5
1
1.5
2
2.5
3
3.5
4
Hispanic White 25%-50%
(N=154)
Hispanic White 50%-75%
(N=254)
Hispanic White ≥75%
(N=519)
Hazard ratio (95%CI)
Subgroups
Variables
N (%)
Univariate Full Model*
HR 95% CI HR 95% CI
Ethnicity
Hispanic White with Native American
ancestry proportion <25%
169 (15.42) Ref - Ref -
Hispanic White with Native American
ancestry proportion between 25%-50%
154 (14.05) 1.94 (1.10-3.40) 1.90 (1.06-3.39)
Hispanic White with Native American
ancestry proportion between 50%-75%
254 (23.18) 1.87 (1.11-3.13) 1.53 (0.86-2.72)
Hispanic White with Native American
ancestry proportion ≥75%
519 (47.35) 2.26 (1.41-3.62) 1.62 (0.92-2.87)
15

Figure 4. Hazard ratios and 95% confidence intervals of the fully adjusted
associations between the risk of developing obesity and Native American ancestry
proportion in Hispanic Whites, compared to Hispanic White with Native American
proportion <25% (N=1,096)*.

*Model adjusted for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking, Spanish questionnaire and follow-up weekly outdoor sports.
(significance level: 0.05)

Because there was no significant dose response (tested for trend, p=0.863)
relationship between the proportion of Native American ancestry among Hispanic White
children and the risk of developing obesity, Native American ancestry proportion groups
with ≥25% Native American ancestry were combined. In the univariate analysis, the risks
of developing obesity for children in group of NAA ≥25% were statistically 2.10 folds
higher compared the group of NAA <25% (HR=2.10, 95%CI=1.33-3.32). After
adjustments for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking, Spanish questionnaire usage and follow-up weekly outdoor
1.9
1.53
1.62
0
0.5
1
1.5
2
2.5
3
3.5
4
Hispanic White 25%-50%
(N=154)
Hispanic White 50%-75%
(N=254)
Hispanic White ≥75% (N=519)
Hazard ratio (95%CI)
Subgroups
16

sports, the risk of obesity in Hispanic children with NAA ≥25% was 1.70 folds higher than
the group with NAA <25% (HR=1.70, 95%CI=1.02-2.84).

Table 4. Association between the risk of developing obesity and Native American
ancestry proportion (NAA≥25% combined) within 1,096 Hispanic children
*Model adjusted for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking, Spanish questionnaire and follow-up weekly outdoor sports.
(significance level: 0.05)

Interaction
Parental education levels and mother’s birth place had significant interaction with
Native American admixture for their associations with the risk of developing obesity
(interaction p=0.023 and 0.04, respectively). No other significant interactions were
detected for other covariates.

Stratified analyses were conducted for mother’s birth place and parental education
level. Table 5 shows that in children with mothers born in the U.S., the risk of developing
obesity was 2.69 folds higher for Hispanic children with NAA between 25-50% (HR=2.69,
95%CI=1.32-5.46), and 2.02 folds higher for Hispanic children with NAA between 50-75%
(HR=2.02, 95%CI=0.94-4.31) , and 1.76 folds higher for Hispanic children with NAA ≥75%
(HR=1.76, 95%CI=0.81-3.86), compared to those with ancestry proportion <25%. No
Variables
N (%)
Univariate Full Model*
HR 95% CI HR 95% CI
Ethnicity
Hispanic White with Native American
ancestry proportion <25%
169 (15.42) Ref - Ref -
Hispanic White with Native American
ancestry proportion ≥25%
519 (84.58) 2.10 (1.33-3.32) 1.70 (1.02-2.84)
17

significant association was observed between Native American ancestry proportion and the
risk of developing obesity among children with mothers born in Mexico.

Table 5. Stratified analysis of association between the risk of developing obesity and
Native American ancestry proportion by mother’s birth place* within 1,096
Hispanic White children
*Model adjusted for asthma, age, overweight, household income, parental education
level, weekly outdoor sports, number of exercise classes taken during the prior year,
second-hand smoking, maternal smoking, Spanish questionnaire and follow-up weekly
outdoor sports. (significance level: 0.05)

Variables N (%) HR 95% CI P value
Mother birth place: US
Hispanic White with Native American
ancestry proportion <25%
135(29.54)
Ref
Hispanic White with Native American
ancestry proportion between 25%-50%
114(24.95)
2.69 1.32-5.46 0.006
Hispanic White with Native American
ancestry proportion between 50%-75%
107(23.41)
2.02 0.94-4.31 0.071
Hispanic White with Native American
ancestry proportion ≥75%
101(22.10)
1.76 0.81-3.86 0.157
Mother birth place: Mexico
Hispanic White with Native American
ancestry proportion <25%
9(1.99)
Ref
Hispanic White with Native American
ancestry proportion between 25%-50%
25(5.52)
0.73 0.09-6.13 0.774
Hispanic White with Native American
ancestry proportion between 50%-75%
111(24.50)
1.04 0.20-5.50 0.962
Hispanic White with Native American
ancestry proportion ≥75%
308(67.99)
1.04 0.21-5.20 0.960
18

Figure 5. Hazard ratios and 95% confidence intervals of the mother birth place
stratified associations between the risk of developing obesity and Native American
ancestry proportion in Hispanic Whites, compared to Hispanic White with Native
American proportion <25% (N=1,096)*.

*Model adjusted for asthma, age, overweight, household income, parental education level,
weekly outdoor sports, number of exercise classes taken during the prior year, second-hand
smoking, maternal smoking, Spanish questionnaire and follow-up weekly outdoor sports.
(significance level: 0.05)

Stratified analyses were also conducted by stratifying the parental education levels as
“completed grade 12 or less” and “more than some college or technical school”. Table 6
showed that for children with parental education level in “completed 12
th
grade or less”,
there was no statistically significant association between the risk of obesity development
and Native American ancestry proportion. For children with parental education level in
“more than some college or technical school”, compared to Hispanic children with NAA
<25%, the risk of developing obesity was 2.25 folds higher for Hispanic children with NAA
between 25-50% (HR=2.25, 95%CI=1.07-4.74), and 2.12 folds higher for Hispanic
2.69
2.02
1.76
0.73
1.04
1.04
0
1
2
3
4
5
6
7
Hispanic White 25%-50%
(N=154)
Hispanic White 50%-75%
(N=254)
Hispanic White ≥75%
(N=519)
Hazard Ratio (95%CI)
Subgroups
US Mexico
19

children with NAA between 50-75% (HR=2.12, 95%CI=0.95-4.75) , and 1.92 folds higher
for Hispanic children with NAA ≥75% (HR=1.92, 95%CI=0.83-4.46).
Table 6. Stratified analysis of association between the risk of developing obesity and
Native American ancestry proportion by parental education level* within 1,096
Hispanic White children
Variables N (%) HR 95% CI P value
Education: Completed grade 12 or less
Hispanic White with Native American
ancestry proportion <25%
35(6.18) Ref
Hispanic White with Native American
ancestry proportion between 25%-50%
46(8.13)
0.65 0.21-2.05

0.462

Hispanic White with Native American
ancestry proportion between 50%-75%
140(24.73)
0.83 0.34-2.04 0.685
Hispanic White with Native American
ancestry proportion ≥75%
345(60.95)
0.73 0.30-1.77 0.492
Education: More than Some college or
technical school

Hispanic White with Native American
ancestry proportion <25%
132(29.07) Ref
Hispanic White with Native American
ancestry proportion between 25%-50%
105(23.13)
2.25 1.07-4.74

0.033

Hispanic White with Native American
ancestry proportion between 50%-75%
99 (21.81)
2.12 0.95-4.75 0.068
Hispanic White with Native American
ancestry proportion ≥75%
118 (25.99)
1.92 0.83-4.46 0.130
*Model adjusted for asthma, age, overweight, household income, parental education
level, weekly outdoor sports, number of exercise classes taken during the prior year,
second-hand smoking, maternal smoking, Spanish questionnaire and follow-up weekly
outdoor sports. (significance level: 0.05)

20

Figure 6. Hazard ratios and 95% confidence interval of parental education level
stratified association between the risk of developing obesity and Native American
ancestry proportion in Hispanic Whites, compared to Hispanic White with Native
American proportion <25% (N=1,096)*.

*Model adjusted for asthma, age, overweight, household income, parental education
level, weekly outdoor sports, number of exercise classes taken during the prior year,
second-hand smoking, maternal smoking, Spanish questionnaire and follow-up weekly
outdoor sports. (significance level: 0.05)

0.65
0.83
0.73
2.25
2.12
1.92
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Hispanic White 25%-50%
(N=154)
Hispanic White 50%-75%
(N=254)
Hispanic White ≥75%
(N=519)
Hazard Ratio (95%CI)
Subgroups
Grade 12 or less More than college or tech school
21

Discussion

In this longitudinal study, we found Hispanic White children with NAA ≥25% have
greater risks of developing obesity compared to Hispanic White children with <25% Native
American admixture. This association was independent of baseline asthma history, age,
overweight status, household income, parental education levels, physical activity, second-
hand smoking, maternal smoking in utero, Spanish questionnaire and follow-up physical
activity. The association between risk of obesity development and Native American
ancestry proportion among Hispanic White children was stronger among children with
their mothers born in U.S. and their parents with education higher than collage or technical
schools.

Two previous studies reported a positive association between obesity risk and Native
American ancestry proportion among Pima Indians (N=7,796) and a Native American
Community (N=846) [14, 15], which support our findings. However, Hao Hu et al found
that individuals with <20% Native American ancestry were 2.5 times more likely to be
obese compared to those with >80% Native American ancestry among Mexican American
adults with an average age of 40 years old in Houston, Texas (N=4,662) [16]. This
inconsistency may be due to the different study designs (longitudinal study vs. cross-
sectional study), where our study examines the risk of developing obesity in childhood
over time, which may provide more insights into early childhood obesity development.
This could also be due to the difference of average European ancestry proportion between
two study populations. In Hao’s study, their subjects had an average around 50.2% of
22

Native American ancestry proportion and 42.7% of European ancestry proportion, which
was different than 64.8% and 28.9% average in our study population. While another study
conducted on adult Hispanic population showed a positive association between BMI and
Native American ancestry which is consistent with our findings[17].

In the stratified analysis by parental education levels, we found that among children
with high parental education, having a larger proportion of Native American ancestry was
associated with higher risk for obesity, and the effect size for the group with NAA between
25-50% was significant. The association for the lower parental education group was in the
opposite direction, and the effect size was not significant. Most of the effect sizes were not
statistically significant after stratification by parental education level due to small sample
size of the reference group. A study showed that lower maternal education level was
associated with less healthy food choices for their children [18]. Therefore, children with
lower parental educational level are more likely to eat unhealthy foods. Strong negative
impact of unhealthy diet on the obesity risk may mask the underlying relationship between
Native American genetic admixture and the risk of developing childhood obesity in the
low education group. More diet information is warranted to address this hypothesis.

This study has several advantages. First, this is a long-term prospective study, which
provides information to support a potential causal relationship. Second, detailed social-
economic status and lifestyle exposures were consistently collected over the entire study
follow-up allowing for proper adjustment for such factors. Third, our novel findings that
Native American ancestry proportion was positively associated with the risk of developing
23

obesity among school-aged children strengthen the necessity to early prevent obesity
among Hispanic white children with higher proportion of Native American Ancestry. Also,
the use of Native American ancestry proportion for each subject rather than self-identified
genetic identity gave more accurate information about individual genetic ancestry.
However, this study also has several limitations. First, we have limited power to detect
interaction due to small sample size in some combinations of education and Native
American ancestry proportion subgroups. The other limitation is that we do not have diet
data collected for this cohort. Study showed that there is a significant association between
healthy dietary pattern and the obesity risk, the more unhealthy food they consumed the
greater the risk of obesity will be [19]. There are some other factors that may lead to biased
results. Physical activity information was less accurate because it was estimated based on
answers from self-reported questionnaires about sports and exercises questions. More
objective measurements such as accelerometers will be need for more accurate
measurement. Also, obesity was classified by BMI percentile rather than direct
measurements of body fat which could lead to some misclassification of obesity among
children since the proportion of body fat increases with age whereas muscle mass decreases,
so that BMI may not reflect the changes in body fat accurately[20]. Another limitation was
that our statistical analysis did not take into account the obesity recurrence during the study
follow-up.

In conclusion, our study has shown that higher Native American Native American
ancestry proportion is associated with higher risk of developing obesity among Hispanic
White children from kindergarten to high school graduation. The association was not
24

explained by the history of asthma diagnosis, age, overweight, household income, parental
education level, weekly outdoor sports, number of exercise classes taken during the prior
year, second-hand smoking, maternal smoking in utero, Spanish questionnaire usage and
exercise during the follow-up period. Our results suggest that Native American ancestry
proportion plays a role in the variation of obesity risk among Hispanic children, a high risk
population for obesity and other metabolic diseases. Early intervention in Hispanic children
with higher proportion of Native American ancestry can make significant contribution in
preventing obesity in this high risk population.

25

References
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obesity in the United States. N Engl J Med, 2014. 370(17): p. 1660-1.
2. Wright, C., A US epidemic: childhood obesity. J Physician Assist Educ, 2010. 21(2):
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3. Flegal, K.M., et al., Prevalence and trends in obesity among US adults, 1999-2008.
JAMA, 2010. 303(3): p. 235-41.
4. Speakman, J.R., Obesity: the integrated roles of environment and genetics. J Nutr,
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obesity traits and to map genes in admixed populations. Nutr Rev, 2004. 62(7 Pt
2): p. S69-74.
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Am J Prev Med, 1996. 12(4): p. 223-4.
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overweight in the United Kingdom and United States. Int J Obes (Lond), 2015.
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9. Liu, J., et al., Acculturation, physical activity, and obesity among Hispanic
adolescents. Ethn Health, 2009. 14(5): p. 509-25.
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10. Richards, T.J. and P.M. Patterson, Native American obesity: An economic model of
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88(3): p. 542-560.
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13. Salam, M.T., et al., Genetic Ancestry and Asthma and Rhinitis Occurrence in
Hispanic Children: Findings from the Southern California Children's Health Study.
PLoS One, 2015. 10(8): p. e0135384.
14. Williams, R.C., et al., Individual estimates of European genetic admixture
associated with lower body-mass index, plasma glucose, and prevalence of type 2
diabetes in Pima Indians. Am J Hum Genet, 2000. 66(2): p. 527-38.
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Hum Biol, 2014. 26(3): p. 347-60.
16. Hu, H., et al., The Relationship between Native American Ancestry, Body Mass
Index and Diabetes Risk among Mexican-Americans. PLoS One, 2015. 10(10): p.
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27

18. Cribb, V.L., et al., Is maternal education level associated with diet in 10-year-old
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2008. 32 Suppl 3: p. S56-9.

Abstract (if available)

Abstract Background: Childhood obesity has become an epidemic in the U.S., and the risk is particularly dramatic in minority populations such as Hispanic Whites, but the individual risk susceptibility varies a lot within the Hispanic population. Previous studies have shown that genetic factors could be one of the major causes of variation in obesity risk among Hispanics. Since the risk of obesity is also high among Native American populations, our study aimed to assess the association between Native American ancestry and the risk of developing obesity among Hispanic White children in the Children’s Health Study (CHS). ❧ Method: 1,718 non-obese children at baseline were included in the analysis. Children were followed from kindergarten to high school graduation. Height and weight were measured by a trained technician at every study visit, and obesity was defined as a BMI above 95% compared to the age and sex-specific Center for Disease Control (CDC) 2000 BMI growth curves. Socio-demographic status, history of respiratory illness, physical activity, parental education levels, second hand smoking exposure, and in utero smoking exposure, and other household characteristics were collected at baseline and every year during the follow-up using CHS questionnaire. Proportional hazards models were used to analyze the association between Native American ancestry proportion which was estimated by ancestry informative markers and the risk of developing obesity during the follow-up. We categorized Native American ancestry proportion into four groups by Native American ancestry proportion among Hispanic Whites as <25%, 25-50%, 50-75% and ≥75% groups. Baseline asthma history, age, overweight, household income, parental education level, physical activity, second-hand smoking, maternal smoking in utero, Spanish questionnaire usage and follow-up physical activity were adjusted for potential confounders. ❧ Results: Univariate analysis showed that compared to the <25% Native American admixture, the risk of developing obesity was significantly higher in Hispanic White children with ≥25% Native American admixture (HR=2.10 95%CI=1.33-3.32). The association remained significant after adjusting for potential confounders (HR=1.70 95%CI=1.02-2.84). Parental education level and maternal birth place significantly modified the association between Native American admixture and the risk of developing obesity during the follow (interaction p=0.023 and 0.04, respectively). Stratified analysis by parental education levels showed that among children in the group that parental education level more than collage or technical school, three groups of Hispanic white children with Native American ancestry 25-50%, 50-75% and ≥75% were associated with around 2.10 folds lower risk of obesity compared to Hispanic white children with Native American ancestry <25% (all p<0.130), and it was statistically significant in the 25-50% group. No significant association was observed among children with parental education level less than high school. Stratified analysis by maternal birth places showed that among children whose mother were born in the U.S., the risk of developing obesity for children with Native American ancestry 25-50%, 50-75% and ≥75% were around 2.10 folds higher compared to Hispanic white children with Native American ancestry <25% (all p<0.157), and it was statistically significant in the 25-50% group. But no significant association was observed between Native American ancestry proportion and the risk of developing obesity among children with mothers born in Mexico. ❧ Conclusion: Native American ancestry ≥25% was associated with higher risk of developing obesity from age 5 to 8 among Hispanic White Children compare to those with Native American ancestry <25%. Such association was greater among children with parental education level lower than high school and with their mothers born in the U.S. These results indicate that Native American Native American ancestry proportion is a risk factor for obesity among Hispanic White children, who were known to have higher risk for obesity compare to other populations. Our results provided inform for future obesity intervention programs. Early intervention in Hispanic children with high proportion of Native American ancestry may reduce the overall obesity burden among Hispanic children and adolescents.

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Asset Metadata

Creator Tang, Chengke (author)

Core Title Native American ancestry among Hispanic Whites is associated with higher risk of childhood obesity: a longitudinal analysis of Children’s Health Study data

School Keck School of Medicine

Degree Master of Science

Degree Program Applied Biostatistics and Epidemiology

Publication Date 06/20/2016

Defense Date 03/25/2016

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag ancestry proportion,childhood obesity,Hispanic White,OAI-PMH Harvest,proportional hazard regression

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Gilliland, Frank (committee chair), Berhane, Kiros (committee member), Habre, Rima (committee member)

Creator Email chengket@usc.edu,tchengke35@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c40-256074

Unique identifier UC11280530

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Legacy Identifier etd-TangChengk-4456-1.pdf

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