Elif Irem Sarihan1, Eduardo Pérez-Palma1, Lisa-Marie Niestroj2, Douglas Loesch3,4,5, Miguel Inca-Martinez1, Andrea R V R Horimoto6, Mario Cornejo-Olivas7,8, Luis Torres9,10, Pilar Mazzetti7,10, Carlos Cosentino9,10, Elison Sarapura-Castro7, Andrea Rivera-Valdivia7, Elena Dieguez11, Victor Raggio12, Andres Lescano11, Vitor Tumas13, Vanderci Borges14, Henrique B Ferraz14, Carlos R Rieder15, Artur F Schumacher-Schuh16, Bruno L Santos-Lobato17, Carlos Velez-Pardo18, Marlene Jimenez-Del-Rio18, Francisco Lopera18, Sonia Moreno18, Pedro Chana-Cuevas19, William Fernandez20, Gonzalo Arboleda20, Humberto Arboleda20, Carlos E Arboleda-Bustos20, Dora Yearout21,22, Cyrus P Zabetian21,22, Timothy A Thornton23, Timothy D O'Connor3,4,5, Dennis Lal1,2,24,25, Ignacio F Mata1,21,22. 1. Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, Ohio, USA. 2. Cologne Center for Genomics, University of Cologne, Cologne, Germany. 3. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA. 4. Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 5. Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 6. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA. 7. Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru. 8. Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru. 9. Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru. 10. School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. 11. Neurology Institute, Universidad de la República, Montevideo, Uruguay. 12. Department of Genetics, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 13. Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto, Brazil. 14. Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil. 15. Departamento de Neurologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. 16. Serviço de Neurologia, Hospital de Clínicas de Porto Alegre and Departamento de Farmacologia, Universidade Federal do Rio Grande do Su, Porto Alegre, Brazil. 17. Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, Brazil. 18. Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Colombia. 19. CETRAM, Facultad de Ciencias Medicas, Universidad de Santiago de Chile, Santiago de Chile, Chile. 20. Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá, Colombia. 21. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. 22. Department of Neurology, University of Washington, Seattle, Washington, USA. 23. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 24. Stanley Center for Psychiatric Research, Broad Institute of MIT & Harvard, Cambridge, Massachusetts, USA. 25. Epilepsy Center & Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Abstract
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.
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.
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