Familial Aggregation of Parkinson Disease and Essential Tremor in Early and Late Onset Parkinson Disease Cohorts

OBJECTIVES: Early-onset Parkinson disease (EOPD) is associated with stronger genetic contributions than late-onset Parkinson disease (LOPD). However, the complex interplay between genetic susceptibility, family history, and environmental factors remains incompletely understood. This study assesses familial aggregation of PD and essential tremor (ET) among relatives of patients with EOPD and compares it with patients with LOPD. METHODS: Patients with EOPD evaluated at the Mayo Clinic were identified, whereas patients with LOPD were identified through the Rochester Epidemiology Project record-linkage system. All cases with symptom onset between 1991 and 2020 were included. DISCUSSION: The higher prevalence of PD and ET family history in the EOPD cohort supports a stronger genetic contribution and may reflect enrichment for high-penetrance monoallelic variants. Conversely, the higher frequency of affected siblings in the LOPD cohort suggests a polygenic inheritance pattern with greater environmental contribution.