Dissertations and Theses

Date of Degree

9-30-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Epidemiology and Biostatistics

Advisor(s)

Mary Schooling

Committee Members

Levi Waldron

Michael Schwarzschild

Subject Categories

Environmental Public Health | Epidemiology | Immune System Diseases | Nervous System Diseases | Public Health

Keywords

Mendelian Randomization, Parkinson's disease, multiple sclerosis, epidemiology, proteins, proteomics

Abstract

Multiple sclerosis (MS) and Parkinson’s disease (PD) are progressively disabling neurologic disorders that profoundly affect quality of life and shorten life expectancy. There is no cure for either disease, and current treatments only alleviate symptoms and may cause serious side effects. The causes of MS and PD are not well understood. Previous epidemiologic studies have documented numerous environmental risk factors for both diseases. However, these studies are inherently prone to bias from confounding which may generate spurious results. The lack of unbiased evidence on environmental causes of MS and PD has been a critical barrier to fully understanding their pathophysiology. Mendelian Randomization (MR), instrumental variable (IV) analysis using genetic instruments, is a powerful tool in epidemiology that can overcome the problem of confounding. The aim of this study is to use MR to identify comprehensively plasma proteins that may be causes of PD and MS. Proteins are involved in numerous biological processes and are frequently dysregulated in diseases, making them a valuable source of information for identifying potential causes of disease. This study will address the critical barrier of bias in studies on causes of MS and PD. Findings may help researchers to better understand the pathophysiology of these diseases, and may also help inform the planning of new interventions and randomized controlled trials (RCTs) for MS and PD.

Available for download on Tuesday, November 15, 2022

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