Neurology · 2026
Familial Aggregation of Parkinson Disease and Essential Tremor in Early and Late Onset Parkinson Disease Cohorts.
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Malfer Lorenzo, Liu Tina, Mullan Aidan, Santoro Emanuela, Lynott Elena B, Troxel Colton E, Derhab Mohamed, Ghoniem Khaled, Ross Owen A, Bower James H, Savica Rodolfo
Аннотация
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.
RESULTS: A total of 732 cases with EOPD and 469 with LOPD were included. EOPD patients were significantly more likely to have a positive family history of PD in parents (proportion ratio [PR] = 1.67, p = 0.049), second-degree relatives (PR = 2.54, p < 0.001), and all family members (PR = 1.63, p < 0.001). Similarly, they had higher frequency of family history of ET (PR = 1.47, p = 0.029). By contrast, patients with EOPD were less likely to have siblings with PD (PR = 0.38, p = 0.009).
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.
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.
RESULTS: A total of 732 cases with EOPD and 469 with LOPD were included. EOPD patients were significantly more likely to have a positive family history of PD in parents (proportion ratio [PR] = 1.67, p = 0.049), second-degree relatives (PR = 2.54, p < 0.001), and all family members (PR = 1.63, p < 0.001). Similarly, they had higher frequency of family history of ET (PR = 1.47, p = 0.029). By contrast, patients with EOPD were less likely to have siblings with PD (PR = 0.38, p = 0.009).
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.