Abstract
High Blood Pressure (HBP) is a leading cause of death in
the United States. The attributed mortality rate of HBP remains at
a high level in recent years. Cigarette smoking is a major
preventable cause of death in U.S. Our study aims to understand
etiology of HBP, including genetic susceptibility of high systolic
and diastolic blood pressure among the Caucasian population as well
as cigarette smoking modification effect on the association between
single nucleotide polymorphisms (SNPs) and blood
pressure.Statistical tests were used to investigate difference
between hypertensive and normotensive study sample. Marginal linear
mixed regression model were conducted to discover association
between main effect, SNP-smoke interaction effect and blood
pressure trait using a genome-wide approach.None of
SNPs were detected significantly associated with SBP from both
additive and genotypic model. Eight SNPs were identified associated
with DBP significantly (FDR Q value < 0.05 with genomic control
applied). Seven SNP-smoking interactions were found to be
significantly associated with SBP from the additive interaction
model and three such significant associations were uncovered from
genotypic model. No smoking modification effect associated with
DBP. In conclusion, current smoking
status could modify the magnitude of SNP-SBP associations, whereas
no evidence supported the similar modify of SNP-DBP
associations.
Table of Contents
Table of Contents
BACKGROUND & INTRODUCTION 1
BURDEN OF HIGH BLOOD PRESSURE & CIGARETTE SMOKING 1
EPIDEMIOLOGY OF HIGH BLOOD PRESSURE 2
GENOMIC EPIDEMIOLOGY STUDIES OF HUMAN DISEASES 4
PREVIOUS GENOMIC EPIDEMIOLOGY STUDIES ASSOCIATE WITH BLOOD
PRESSURE 6
METHODS 10
STUDY DESIGN 10
HYPOTHESIS 10
STUDY SAMPLE 10
STATISTICAL ANALYSIS 11
GENOMIC CONTROL 14
MULTIPLE TESTING ADJUSTMENTS: 15
RESULTS 16
DESCRIPTIVE STATISTICS AND STATISTICAL TESTS 16
REGRESSION ANALYSIS OF MAIN GENETIC EFFECT 17
REGRESSION ANALYSIS FOR G×E INTERACTION 18
DISCUSSION 20
REFERENCE 24
TABLES 33
Table 1. Study population Characteristics 33
Table 2. Statistical tests for influence factors between
hypertensive and non-hypertensive group 34
Table 3. Result of genotypic SNP-DBP association no
interaction model (model 3) 35
Table 4 Top 10 significant SNP-Smoke interaction that
associate with SBP form additive interaction model (model2)
36
Table 5 Top 10 significant SNP-Smoke interaction that
associate with SBP form genotypic interaction model (model4)
37
FIGURES AND FIGURE LEGENDS 38
Figure 1. Q-Q plot for Additive No-Interaction Mode (model 1)
38
Figure 2. Q-Q Plot for Genotypic No-Interaction Model (model
1) 38
Figure 3. Q-Q plot for Additive No-Interaction Model (model 2)
39
Figure 4. Q-Q plot for Genotypic No-Interaction Model (model
2) 39
Figure 5. Q-Q plot for Additive Interaction Model (model 3)
40
Figure 6. Q-Q plot for Genotypic Interaction Model (model 3)
40
Figure 7. Q-Q plot for Additive Interaction Model (model 4)
41
Figure 8. Q-Q plot for Genotypic Interaction Model (model 4)
41
APPENDICES 42
About this Master's Thesis
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