Toward a phenome-wide view of Parkinson's disease

Background and ObjectivesMany studies have examined the relation between PD and environmental variables serially --- one candidate association at a time. In the real world however, both environmental exposures and patients are much more complex, including correlated environmental exposures, polypharmacy, and complex comorbidities. Here we begin to characterize a holistic view of environmental, health, and pharmacological traits linked to patients with PD. MethodsThe Harvard Biomarkers Study (HBS) is a large case-control study of PD patients and healthy controls that includes an extensive questionnaire covering past medical and social history data and is thus well-suited for such an exploratory study. Sixty-four environmental, pharmacological, and clinical features were evaluated for associations with PD using logistic regression analysis with backward elimination. ResultsMale gender, coronary artery disease, depression, anxiety, restless leg syndrome, head trauma, ibuprofen use, co-enzyme Q10 use, and vitamin D supplementation were significantly positively associated with PD. By contrast, asthma/chronic obstructive pulmonary disease (COPD), naproxen, ezetimibe, and smoking were significantly negatively associated with PD. DiscussionThis study shows that unbiased, data-rich exploration of the Parkinson phenome has the promise to uncover, prioritize, and clarify associations between environment, multi-system health phenotypes, and PD in a patient-centric manner. Associations with coronary artery disease, mood disorders, and the cholesterol-absorption inhibitor ezetimibe were revealed that have been largely neglected in traditional hypothesis-driven investigations. Interestingly, asthma/COPD was inversely associated with PD, and this was independent of smoking history. Furthermore, well-established associations were confirmed for male gender, smoking, head trauma, and restless legs syndrome.