Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7). Conclusions: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.
Bibliographical noteFunding Information:
: Recruitment of LARGE‐PD participants was funded by an International Research Program Grant from the Parkinson's Disease Foundation (2010‐2012), and this work was funded by a Stanley Fahn Junior Faculty Award from the Parkinson's Foundation. This work was also supported by a research grant from the American Parkinson's Disease Association, with resources and the use of facilities at the Veterans Affairs Puget Sound Health Care System. M. J. ‐D. ‐R. and C. V. ‐P. were supported by the Committee for Development and Research (Comite para el desarrollo y la investigación‐CODI)‐Universidad de Antioquia grant 2020‐31455. Funding agencies
Dr. Horimoto is supported by grants from the Parkinson's Disease Foundation. Dr. Lescano is supported by grants from the Parkinson's Disease Foundation. Dr. Borges reports honoraria from ACHÉ Laboratorios Farmacéuticos. Dr. Rieder reports financial support provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). Dr. Velez‐Pardo and Dr. Jimenez‐Del‐Rio are supported by a CODI grant. Ms. Yearout is supported by grants from American Parkinson's Disease Association, Parkinson's Disease Foundation for this research, as well as grants from Department of Veterans Affairs, NINDS, National Institutes of Health, Michael J. Fox Foundation unrelated to this research. Dr. Zabetian is supported by grants from Parkinson's Foundation and salary from the Department of Veterans Affairs for this research, as well as grants from the National Institutes of Health, Department of Veterans Affairs, and American Parkinson Disease Association unrelated to this research. Dr. Thornton is supported by grants from Parkinson's Disease Foundation. Dr. O’Connor is supported by grants from the National Institutes of Health. Dr. Mata is supported by grants from the Department of Veterans Affairs, Parkinson's Foundation, American Parkinson's Disease Association, Michael J. Fox Foundation, and National Institutes of Health.
© 2020 International Parkinson and Movement Disorder Society
- Latin America
- Parkinson's disease
- copy number variants