Integrating human brain transcriptomes and proteomes with genome-wide association data identifies risk genes shared between depression and Alzheimer’s disease Público

Abstract

Depression increases the risk for Alzheimer’s disease (AD) in prospective epidemiological studies and recent evidence has shown a significant genetic correlation between depressive symptoms and AD. These lines of evidence suggest the possibility of shared pathophysiology and/or genetic liability between depression and AD. The first step toward deciphering the underlying mechanisms is to test the genetic correlation and explain the implications of a shared genetic basis between depression and AD. We show that there is a genetic basis to this association using data from the latest genome-wide association studies of depression and AD, respectively. Furthermore, we demonstrate that depression contributes to AD pathogenesis at the genetic level using Mendelian randomization. Lastly, we identified 46 brain transcripts and 8 brain proteins that underlie the contribution of depression to AD. These brain transcripts and proteins were significantly associated with AD pathologies, cognitive trajectory, and AD clinical diagnosis at FDR <0.05. Our study suggests that depression has a consistent causal role on AD, and we nominate 54 genes as potential mediators for future mechanistic studies to effectively treat these two illnesses

Table of Contents

Chapter 1: Depression and risk of developing Alzheimer’s disease

Reference

Chapter 2: Depression contributes to Alzheimer’s disease through shared genetic risk

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Reference

Chapter 3: Conclusions and recommendations for future studies

About this Master's Thesis

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Genetics and Molecular Biology
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Bioinformatics Biology, Genetics Biology, Neuroscience
Palavra-chave	Genome-wide association study (GWAS), single nucleotide polymorphism (SNP), Alzheimer's disease (AD), linkage disequilibrium score (LDSC) regression, Mendelian randomization (MR),and quantitative trait loci (QTL)
Committee Chair / Thesis Advisor	Thomas S. Wingo, Emory University Aliza P. Wingo, Emory University
Committee Members	Nicholas Seyfried, Emory University Victor Corces, Emory University Karen N. Conneely, Emory University David J. Culter, Emory University

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