Criteria for Cases: Cases were enrolled prospectively from the clinical practice of the Department of Neurology of the Mayo Clinic in Rochester, MN, from June 1996 through May 2004. They all resided within Minnesota or one of the surrounding four states (Wisconsin, Iowa, South Dakota, or North Dakota). All cases underwent a standardized clinical assessment performed by a neurologist sub-specialized in movement disorders. Cases had at least two of four cardinal signs of parkinsonism (rest tremor, rigidity, bradykinesia, and/or postural instability) and no features atypical for PD (such as unexplained upper motor neuron signs or cerebellar signs). When non-motor manifestations such as dysautonomia or dementia were present, they were mild and occurred late in the disease course. Subjects with secondary causes of parkinsonism (e.g., history of neuroleptic exposure, encephalitis, or multiple strokes) were excluded. All patients treated with a daily dosage total of 1 g of levodopa (in combination with carbidopa) had a more than minimal improvement in parkinsonism symptoms and signs.

Criteria for Controls: Unaffected siblings of cases, matched on gender when able then on closest age at study (tier 1); or unrelated population controls, matched on gender and age at study (tier 2). All controls screened negative for parkinsonism via telephone interview, or were confirmed to not have parkinsonism via clinical assessment.