A clinical genetic study of Parkinson's disease

Abstract

We used a family history questionnaire, semi-structured interview, and personal examination of secondary cases to collect data on the prevalence of Parkinson's disease (PD) in relatives of patients seen consecutively for 1 year and assessed the proportion of secondary cases of PD as a function of pedigree completeness. Survival analysis methods were applied to estimate the lifetime risk and age-at-onset distribution of PD among first-degree relatives of probands. When we considered siblings of probands with affected parents, the cumulative risk increased significantly over siblings of probands without affected parents, suggesting significant familial aggregation in a subset of randomly ascertained families. We further analyzed 80 multicase families with two or more affected individuals. Age-adjusted segregation ratios approaching 0.5 and similar proportions of affected parents and siblings, as well as the distribution of ancestral secondary cases, were compatible with an autosomal dominant mode of inheritance with reduced penetrance in a subset of PD