The Age at Onset of LRRK2 p.Gly2019Ser Parkinson's Disease Across Ancestries and Countries of Origin.

Same LRRK2 G2019S founder variant with variable expressivity by ancestry (North African, Ashkenazi Jewish, European)

922 LRRK2 p.Gly2019Ser carriers from the GP2 program were included to analyze age-at-onset differences by ancestry. North African ancestry carriers develop disease 5 years earlier (HR = 1.48) and Ashkenazi Jewish carriers 5 years later (HR = 0.61) compared to Europeans. Tunisian patients show the highest cumulative risk (HR = 2.57). These data modify genetic counseling according to patient geographic origin.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

These multi-ancestry data on LRRK2 G2019S have a direct consultation implication: penetrance and age-at-onset counseling can no longer be uniform for this variant, despite being classically presented as the most frequent in genetic PD. The environmental or polygenic component modulating expressivity remains to be elucidated.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 7/10