Date of Award

January 2023

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Andrew T. DeWan

Abstract

Background: Alzheimer’s disease (AD) has been rising globally, making it important to understand risk factors. Depression has been identified as a risk factor in epidemiological studies and meta-analysis. The possible mechanism could be pleiotropic. This study sought to identify the pleiotropic SNPs associated with depression and AD so that can understand the relationship between the two diseases more evident.Methods: The sample was from the UK biobank population, using the White European subpopulation. Depression was defined using self-reported depression status and electronic medical records. Proxy AD was defined by biological mother and father’s AD status. Two univariate association analysis was conducted using a linear mixed model in REGENIE. A p-value comparison was conducted for both analyses. Linkage disequilibrium (LD) clumping was conducted using a four MB region surrounding the index variant and an r2 threshold of 0.2. Results: The study had 406,7394 individuals in the depression sample and 409,704 individuals in the AD sample. The univariate analysis for depression identified five genome-wide significant SNPs, and the univariate analysis for AD identified 1,319 genome-wide significant SNPs. The p-value comparison found that 36 genome-wide significant SNPs for AD were genome-wide nominal for depression, with SNPs chromosome 8 having p-values for depression less than 0.001. The LD clumping identified a region in chromosome 19 associated with genes APOE and TOMM40. The leading SNP was rs2075650 and associated with the two phenotypes. Conclusion: The study found SNPs associated with depression and AD. Furthermore, SNP rs2075650 on chromosome 19 seems promising in understanding the relationship between depression and AD. Further studies must be conducted to understand the association that can lead to prevention methods.

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This is an Open Access Thesis.

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