Category: Parkinson's Disease: Genetics
Objective: To assess the CNV burden in a cohort of Latin American Parkinson’s disease (PD) patients and controls.
Background: Despite the fact that PD prevalence is the highest among Hispanics [1] (16.6 per 100,000), there have been no large genetic studies conducted for PD etiology. This is especially true for copy number variants (CNVs) which are also understudied in all PD patients. To address this issue, we performed a CNV analysis in the Latin American Research Consortium on the Genetics of PD (LARGE-PD) [2].
Method: We screened a total of 1,503 participants who were recruited from Peru (n = 721), Colombia (n = 351), Brazil (n = 227), Uruguay (n = 191), and Chile (n = 13) as part of an ongoing collaborative effort in LARGE-PD. We genotyped 1,779,819 single nucleotide polymorphisms (SNPs) using the Illumina Multi-Ethnic Global Array. After quality control procedures, the final dataset included 1,342 samples with 731 PD cases and 611 controls. CNVs were called using PennCNV software and annotated both with genes previously known to be associated with PD, and with RefSeq genes.
Results: We found no difference between PD patients vs controls for CNV burden in nongenic regions (OR: 0.82 [0.57 – 1.18], P = 0.28) or genic regions (OR: 1.01 [0.76 – 1.34], P = 0.93). Burden of large CNVs that were > 1Mb (OR: 1.55 [0.86 – 2.83], P = 0.15) was also similar between patients and controls. However, PD patients were significantly enriched with CNVs overlapping known PD genes (OR: 3.66 [1.56 – 9.67], P = 0.005). This signal was driven by CNVs in PARK2 in 19 patients and SNCA in 2 patients. Patients carrying a CNV in PARK2 had earlier onset disease compared to patients with CNVs in other genes (mean age of onset: 32.3 vs 54.8, 95% CI: 14.8 – 30.1, P < 0.001).
Conclusion: Here we present the first-ever CNV analysis in Latin American PD patients. We found that PD patients are significantly enriched with CNVs affecting known PD genes. We also identified that out of 249 patients with early-onset disease, 5.6% carried a CNV in PARK2 in our cohort. In sum, our work provides a new perspective and enriches current knowledge about CNVs in underrepresented populations. Expanding the diversity of genetic studies is necessary both to make discoveries applicable to specific patient populations and to reduce health disparities in the era of precision medicine.
References: 1. Van Den Eeden, S. K. et al. Incidence of Parkinson’s Disease: Variation by Age, Gender, and Race/Ethnicity. Am. J. Epidemiol. 157, 1015–1022 (2003). 2. Zabetian, C. P. & Mata, I. F. LARGE-PD: Examining the genetics of Parkinson’s disease in Latin America. Mov. Disord. 32, 1330–1331 (2017).
To cite this abstract in AMA style:
E.I Sarihan, E. Pérez-Palma, L.M Niestroj, D. Loesch, M. Seyfi, M. Inca-Martinez, A. Horimoto, M. Cornejo-Olivas, L. Torres, P. Mazzetti, C. Cosentino, E. Dieguez, V. Raggio, A. Lescano, V. Tumas, V. Borges, H.B Ferraz, C. Rieder, A. Schumacher-Schuh, B.L Santos-Lobato, C. Velez-Pardo, M. Jimenez-Del-Rio, F. Lopera, P. Chana-Cuevas, W. Fernandez, G. Arboleda, H. Arboleda, C.E Arboleda-Bustos, D. Yearout, C.P Zabetian, T. Thornton, T.D O’Connor, D. Lal, I.F Mata. The First-Ever CNV Analysis in Latin American Parkinson’s Disease Patients [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/the-first-ever-cnv-analysis-in-latin-american-parkinsons-disease-patients/. Accessed May 17, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-first-ever-cnv-analysis-in-latin-american-parkinsons-disease-patients/