Familial aggregation of Parkinson disease: A comparative study of early-onset and late-onset disease

Context: It is unclear whether late-onset Parkinson disease (PD), which is the most typical and most common form of the disease, has a familial component. Evidence for familial aggregation is key to whether research should focus on gene discovery or search for environmental factors. Objective: To investigate familial aggregation of early-onset and late-onset PD separately. Methods: Using survival methods, age-specific risk of PD was calculated and compared for 525 parents and siblings of 117 patients with early-onset PD, 1642 parents and siblings of 343 patients with late-onset PD, and 522 parents and siblings of 114 controls. The index patients were ascertained from a movement disorder clinic. Spouses and friends served as controls. Results: Compared with the relatives of controls, age-specific risk of PD was increased 7.76-fold in the relatives of patients with early-onset disease (P<.001) and 2.95-fold in the relatives of those with late-onset disease (P=.02). Conclusions: Late-onset PD has a significant familial component. The magnitude of recurrence risk to relatives suggests a genetic etiology, without ruling out the possibility of a coexisting environmental component.