Date of Award

January 2022

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Andrew DeWan

Abstract

This study sought to characterize patterns of pleiotropy at the genome-wide level between Body Mass Index (BMI) and Systolic Blood Pressure (SBP) associated with the same single nucleotide polymorphism (SNP). First, SNPs associated with BMI and SBP were identified using a dataset of unrelated individuals in the UK Biobank database. Second, SNPs that were independently associated with both traits were subsetted based on a set of significance threshold categories. Lastly, mediation analyses were conducted for each of the subsetted SNPs in order to characterize observed patterns of pleiotropy for BMI and Systolic BP. Many potentially novel genetic loci that exhibit genetic pleiotropy for BMI and SBP were discovered through the GWAS portion of the analysis. The results of the mediation analyses did not show clear evidence of biological pleiotropy, but provided evidence of mediation for each cross-phenotype associated SNP analyzed as there was no instance where the association between the mediator, exposure, and outcome had a non-significant indirect effect. This observed genome-wide mediated pleiotropy is likely due to confounding. However, a pattern was observed where the significant direct effect only appeared when the magnitude of the difference in p-value between the association with mediator and outcome was relatively small (less than about 8 orders of magnitude), suggesting that the effect sizes of the SNP on both phenotypes must be equivalent in order to have a significant direct effect.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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