Genome-wide identification of DNA methylation associated with Systolic and Diastolic Blood Pressures among African Americans Open Access

Zaharoff, Alexander (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/fq977v39c?locale=en%255D
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Abstract

Hypertension is a major risk factor for numerous chronic health diseases. This study aims to further the understanding of the gene-environment interaction related to hypertension. The underlying molecular mechanisms that affect blood pressure measurements will be evaluated. By conducting an epigenome-wide association study (EWAS) of 972 African Americans from Jackson, Mississippi we identified novel methylation sites that were associated with systolic and diastolic blood pressures. After correcting for confounders and multiple testing, two methylation sites were found to be statistically significantly associated with systolic blood pressure. These sites were located on the CCDC25 gene (p-value = 1.5x10-7, FDR = 0.004) and COX7A2L gene (p-value = 1.5x10-6, FDR = 0.020). Findings from this epigenomic study of African Americans may lead to a more comprehensive understanding of hypertension.

Table of Contents

BACKGROUND................................................................................................... 1 INTRODUCTION................................................................................................... 3 METHODS......................................................................................................... 8 STUDY SAMPLE................................................................................................... 8 PHENOTYPE DATA................................................................................................ 8 MEASUREMENT OF DNA METHYLATION..................................................................... 9 DNA METHYLATION DATASET................................................................................. 9 STATISTICAL METHODS........................................................................................ 9 PRINCIPAL COMPONENT ANALYSIS.......................................................................... 11 RESULTS......................................................................................................... 13 DISCUSSION.................................................................................................... 15 STRENGTHS AND LIMITATIONS.............................................................................. 18 FUTURE DIRECTIONS........................................................................................ 20 REFERENCES................................................................................................... 22 TABLES.......................................................................................................... 29 FIGURES AND FIGURE LEGENDS......................................................................... 31 APPENDICES................................................................................................... 34

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