Genetic Epidemiology of Parkinson's Disease

[unreadable] DESCRIPTION (provided by applicant): In the first funding period, we compared the risk of PD in relatives of 221 PD patients with age at onset (AAO) 50 and 409 controls. The magnitude of increased risk of relatives of PD cases vs. controls was similar in early-onset cases (RR: 2.9, 95%C1: 1.6-5.0) and late onset cases (RR: 2.7, 95%CI: 1.6-4.4). However in families of early-onset cases, the degree of increased risk was much greater in siblings (RR: 7.9, 95%C1: 2.5-25.5) than in parents (RR: 1.7, 95% CI: 0.9-3.3), consistent with an autosomal recessive contribution to inheritance. In late-onset families, risk was elevated in both parents and siblings, inconsistent with a recessive model. Mutations in the parkin gene have emerged as the most important causative or risk-raising factor in early-onset PD. In this second competitive renewal application, we have redesigned our study to make optimal use of 300 early onset cases already recruited at the Columbia site (200 not yet screened for parkin mutations) and the 40 PD cases with parkin mutations we have already identified. We will join with investigators at 7 other sites who will contribute an additional 600 cases with age of onset