Genome-wide gene-smoking interaction of Systolic and Diastolic blood pressure among Caucasians Público
Hu, Wenruo (2013)
Published
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
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