Genomic Landscape of Early-Onset and Familial Latin American Parkinson’s Patients

Authors:
Preprint
Publisher website
Google Scholar
Abstract
Background: Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is commonly thought of as an aging and sporadic disease; however, 5-14% of individuals experience disease onset before the age of 50 years (early-onset PD; EOPD) and about 20% have a positive family history. In the case of both EOPD and people with a family history of PD, evidence suggests higher rates of a disease-causing genetic contribution. Objectives: Our goal was to perform a variant screening of seven PD-related genes and 21 genes associated with related parkinsonian disorders to identify pathogenic/likely pathogenic variants and variants of uncertain significance within EOPD and family-history-positive individuals within the Latin American Research Consortium on the Genetics of PD (LARGE-PD). Methods: We performed short-read whole-genome sequencing on a subset of 263 individuals with EOPD and/or a familial history of PD who had no known pathogenic PD variant in genotyping data. Results: Of the analyzed individuals, a monogenic burden in primary and secondary PD genes due to pathogenic or likely pathogenic variants for PD was observed in 4.7%, an additional 5.5% had pathogenic or likely pathogenic variants for Gaucher’s disease, and 2.7% had known risk variants in GBA1 . Conclusions: By expanding the reported spectrum of disease-associated variants in a Latin American population, we identified previously unreported or underrepresented variants that would likely be missed by array-based or targeted screening approaches and contribute to the characterization of EOPD and familial PD in Latin America.
Funding Information
  • Michael J. Fox Foundation (MJFF-026283)
  • Parkinson's Foundation (PDGENE-1333334)
  • Alzheimer's Disease Sequencing Project (5U01AG076482-03)
  • VA Puget Sound Health Care System (5I01ABX005978-2)
  • Chan Zuckerberg Initiative (CZIF2002-007045)
  • American Parkinson Disease Association (1282087)
  • Fulbright Colombia
  • Ministry of Science, Technology and Innovation of Colombia

This publication has 31 references indexed in Scilit: