Genome-wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Abstract

BackgroundParkinsons disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinsons disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinsons disease patients. ObjectivesTo understand the genome-wide burden of copy number variants in Latinos and its association with Parkinsons disease. MethodsWe used genome-wide genotyping data from 747 Parkinsons disease patients and 632 ancestry matched controls from the Latin American Research Consortium on the Genetics of Parkinsons disease. ResultsGenome-wide copy number burden analysis showed no difference between patients vs. controls, whereas patients were significantly enriched for copy number variants overlapping known Parkinsons disease genes compared to controls (Odds Ratio: 3.97 [1.69 - 10.5], P = 0.018). PARK2 showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared to patients with other copy number variants (median age at onset: 31 years vs. 57 years, P = 7.46 x 10-7). ConclusionsWe found that Parkinsons disease patients are significantly enriched with copy number variants affecting known Parkinsons disease genes. We also identified that out of 250 patients with early-onset disease, 5.6% carried a copy number variant on PARK2 in our cohort. Our study is the first to analyze genome-wide copy number variants association in Latino Parkinsons disease patients and provides insights about this complex disease in this understudied population.