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Hughes, Katherine

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    Dietary and Genetic Risk Factors for Parkinson's Disease
    (2016-04-25) Hughes, Katherine; Ascherio, Alberto; Rimm, Eric B.; Wang, Molin; Weisskopf, Marc G.
    Parkinson’s disease (PD) is the second most common neurodegenerative disease. Motor symptoms typically do not manifest until significant neuronal loss has already occurred, highlighting the need for early detection and prevention. In this dissertation, we sought to improve our understanding of PD epidemiology by studying associations between potential modifiable risk factors, including antioxidant vitamins, dairy products, and urate, and PD risk. We conducted prospective analyses within three large cohort studies: the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort. Across all analyses, PD cases were identified via biennial questionnaires and confirmed through medical record review by neurologists specializing in movement disorders. In our first two aims, we used Cox proportional hazards models to calculate relative risks of PD according to cumulative average intakes of foods and nutrients of interest. In aim 1, we found no associations between intake of vitamin E, vitamin C, or carotenoids and risk of PD. In our second aim, we found that low fat dairy intake was associated with increased PD risk, and that this association appeared to be driven by an increased risk of PD associated with skim and low-fat milk intake. The results of a meta-analysis including previously conducted prospective investigations of milk intake and PD risk suggested a relative risk of PD comparing extreme milk intake levels of 1.80 (95% CI 1.44-2.25). In our third aim, although a large body of research suggests that higher urate levels could be protective against PD risk and progression, we found that genetic variants in the SLC2A9 gene that influence circulating urate levels were not associated with risk of PD. Our analyses suggest that while antioxidant vitamins are unlikely to alter PD risk, dairy products may represent an important modifiable PD risk factor. Whether dairy products also alter rates of PD progression or conversion from premotor PD to clinical PD are important, answerable questions. Finally, the results of our third analysis suggest that genetic variants associated with plasma urate levels are not associated with PD risk; however, larger studies are needed to confirm these results.