Year: 2026
Type: preprint
Study design: Observational Study
Abstract: 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.
Source: medRxiv
Authors: Emily Waldo, Henry Mauricio Chaparro-Solano, Mariam Isayan, Thiago Peixoto Leal, Felipe Duarte-Zambrano, Miguel Inca-Martinez, Janvi Ramchandra, Maria Rivera Paz, Mary B. Makarious, Carlos Hernandez, Emilia M Gatto, Natalia Gonzalez Rojas, Martin Emiliano Cesarini, Bruno Lopes Santos-Lobato, Grace Helena Letro, Jorge Luis Orozco, Beatriz Munoz Ospina, Pedro Chana-Cuevas, Natalia Andrea Rojas, David Aguillon, Valentina Muller, Pedro Braga-Neto, Mayela Rodríguez-Violante, Amin Cervantes-Arriaga, Artur F S Schuh, Mario Cornejo-Olivas, Koni Mejia Rojas, Cintia Armas, Ángel Viñuela, Alan Osvaldo Espinal Martinez, Vitor Tumas, Vanderci Borges, Cesar Luis Avila, Patricio Olguin, Sarael Alcauter, Marcelo Kauffman, Dolores Gonzalez-Moron, Susana Lissette Peña, Ignacio F. Mata
Institutions: Cleveland Clinic, Cleveland Clinic Research, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Morehouse School of Medicine, University of California San Diego, Universidad del Desarrollo, Clínica Alemana, Universidade Federal do Pará, Pontifícia Universidade Católica de Campinas, Fundación Valle del Lili, Universidad Icesi, Universidad de Santiago de Chile, Universidad de Antioquia, Hospital de Clínicas "José de San Martín", Universidade Estadual do Ceará, Universidade Federal do Ceará, Instituto Nacional de Neurología y Neurocirugía, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Universidad Científica del Sur, Instituto Nacional de Ciencias Neurológicas, Universidade de São Paulo, Universidade Federal de São Paulo, National University of Tucumán, Consejo Nacional de Investigaciones Científicas y Técnicas, University of Chile, Universidad Nacional Autónoma de México, Hospital Ramos Mejía, Universidad Dr. Andrés Bello
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Identifying novel Parkinson'Âs disease genes exploring understudied Latino populations, G358659287, Additional Sequencing for the Alzheimer Disease Sequencing Project (ADSP) the Follow-Up Study (FUS), The Diverse Population Initiative, Unraveling subcontinental ancestries across Africa, Americas and Europe, and implications for admixture/association mapping of complex traits
OpenAlex ID: W7214028259