Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

The study analyzed genetic data from 38,365 individuals from 11 different ancestries, including 23,242 patients with Parkinson's disease, 4,729 patients with atypical parkinsonism, and 10,394 healthy controls. Researchers examined 12 known pathogenic loci with repeat expansions and identified pathogenic expansions in 62 patients and 5 controls across seven genes. ATXN2 gene expansions were most frequently observed in Parkinson's disease and occurred in African, East Asian, European, and Middle Eastern ancestries. In the European population, individuals with 32 or more ATXN2 repeats had more than four-fold increased disease risk. The majority of expansions (over 92 percent) contained CAA interruptions within the CAG sequence. Patients with pathogenic ATXN2 and ATXN3 expansions most often presented with typical Parkinson's disease features but showed earlier disease onset and strong family history.